Clinical Immunotherapeutics

, Volume 3, Issue 5, pp 362–385

Immunology of Head and Neck Cancer

Prospects for Immunotherapy
  • John W. Hadden
Review Article Treatment Review

Summary

Patients with squamous cell cancer of the head and neck region frequently have cell-mediated immune defects and anergy, which progress with disease. T lymphocytopenia and dysfunction, monocyte dysfunction, prostaglandins, antigen-antibody complexes, serum and cell suppressive factors, radiation therapy and poor nutrition with zinc deficiency all play a role. However, cell-mediated immunoreactivity to tumour is manifest in the majority of patients in blood and regional nodes, and in the tumour itself by tumour-infiltrating lymphocytes. Lymphocytes from these sources cloned in the presence of interleukin-2 ± tumour extracts show relatively specific cytotoxicity against squamous cell cancer. Humoral immunity is intact, and increased IgA levels and antibodies reactive to tumour antigens are common. Tumour-associated antigens detected in tumour and serum include carcinoembryonic antigen, tumour polypeptide antigen, squamous cell cancer antigen, tumour antigen-4 and various mucin antigens. The mucin antigens, in particular, elicit T cell cytotoxicity.

Immunotherapeutic efforts in head and neck squamous cell cancer should logically employ T cell adjuvants, contrasuppression and immunorestoration. Nonspecific stimulation with bacille Calmette-Guérin (BCG), levamisole and other agents has not been successful. Encouraging results have been observed in limited trials with indomethacin, plasmapheresis and thymic peptides. Early trials with local administration of low dosages of interferon-α, natural interleukin-2 and a natural interleukin mixture have produced partial and complete regressions with no toxicity, with intense leucocyte infiltration indicating cell-mediated immunity. On the contrary, treatment with high dosages of recombinant interferon-α and interleukin-2 has yielded few responses with considerable toxicity. Combination strategies are warranted to improve upon this initial immunotherapeutic effort.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Katz A. Manual of otolaryngology: head and neck therapeutics. Philadelphia: Lea & Febinger, 1986Google Scholar
  2. 2.
    Boring CC, Squires TS, Tong T, et al. Cancer statistics, 1994. CA Cancer J Clin 1994; 44: 7–26PubMedCrossRefGoogle Scholar
  3. 3.
    Chretien PB. Unique immunobiological aspects of head and neck squamous carcinoma. Can J Otolaryngol 1975; 4: 222–35Google Scholar
  4. 4.
    Wanebo HJ. Immunobiology of head and neck cancer: basic concepts. Head Neck Surg 1979; 2: 42–55PubMedCrossRefGoogle Scholar
  5. 5.
    Browder JP, Chretien PB. Immune reactivity in head and neck squamous carcinoma and relevance to the design of immunotherapy trials. Semin Oncol 1977; 4: 431–9PubMedGoogle Scholar
  6. 6.
    Dichtel WJ. Immunologic aspects of head and neck cancer. Ear Nose Throat J 1981; 60: 97–106PubMedGoogle Scholar
  7. 7.
    Wolf GT. Head and neck tumor immunology: an overview. Proceedings of the 2nd International Academic Conference on Immunobiology, Histophysiology, and Tumor Immunology in Otolaryngology: Amsterdam. Kugler Publications, 1987: 343–54Google Scholar
  8. 8.
    Wolf GT. Aging, the immune system, and head and neck cancer. Geriatric Otorhinolaryngol 1988; 23: 158–65Google Scholar
  9. 9.
    Gaze MN, Wilson JA. Head and neck tumor immunology. Clin Otolaryngol 1988; 13: 495–9PubMedCrossRefGoogle Scholar
  10. 10.
    Vlock DR. Immunobiologic aspects of head and neck cancer: clinical and laboratory correlates. Head Neck Cancer 1991; 5: 797–819Google Scholar
  11. 11.
    Katz AE. Update on immunology of head and neck cancer. Otolaryngol Clin North Am 1993; 77: 625–31Google Scholar
  12. 12.
    Wustrow TP, Issing WJ. Immune defects in patients with head and neck cancer. Anticancer Res 1993; 13(6): 2507–19PubMedGoogle Scholar
  13. 13.
    Cerezo L, Millan I, Torre A, et al. Prognostic factors for survival and tumor control in cervical lymph node metastases from head and neck cancer. Cancer 1992; 69: 1224–34PubMedCrossRefGoogle Scholar
  14. 14.
    Tannock IF, Browman G. Lack of evidence for a role of chemotherapy in the routine management of locally advanced head and neck cancer. J Clin Oncol 1986; 4: 1121–6PubMedGoogle Scholar
  15. 15.
    Bingham HG. Adjuvant chemotherapy. Surg Clin North Am 1986; 66: 183–8PubMedGoogle Scholar
  16. 16.
    Taylor IV SG. Head and neck cancer. In: Pinedo HM, Longo DL, Chabner BA, editors. Cancer chemotherapy and biological response modifiers. Oxford: Elsevier, 1992: 440–54Google Scholar
  17. 17.
    Wolf GT, Hudson JL, Peterson KA, et al. Lymphocyte subpopulations infiltrating squamous carcinomas of the head and neck: correlations with extent of tumor and prognosis. Arch Otolaryngol Head Neck Surg 1986; 95: 142–52Google Scholar
  18. 18.
    Department of Veterans Affairs Laryngeal Cancer Study Group. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. N Engl J Med 1991; 324: 1685–90Google Scholar
  19. 19.
    Eilber FR, Morton DL. Impaired immunologic reactivity and recurrence following cancer surgery. Cancer 1970; 25: 362–7PubMedCrossRefGoogle Scholar
  20. 20.
    Pinsky CM, Wanebo HJ, Mike V, et al. Delayed cutaneous hypersensitivity reactions and prognosis in patients with cancer. Ann NY Acad Sci 1976; 276: 407–10PubMedCrossRefGoogle Scholar
  21. 21.
    Maisel RH, Ogura JH. Abnormal dinitrochlorobenzene skin sensitization: a prognostic sign of survival in head and neck squamous cell carcinoma. Laryngoscope 1973; 2012–9Google Scholar
  22. 22.
    Catalona WJ, Chretien PB. Abnormalities of quantitative dinitrochlorobenzene sensitization in cancer patients: correlation with tumor stage and histology. Cancer 1973; 31: 353–6PubMedCrossRefGoogle Scholar
  23. 23.
    Twomey JJ, Douglass CC, Norris SM. Inability of leukocytes to stimulate mixed leukocyte reactions. J Natl Cancer Inst 1973; 51: 345–9PubMedGoogle Scholar
  24. 24.
    Lundy J, Wanebo H, Pinsky C, et al. Delayed hypersensitivity reactions in patients with squamous cell cancer of the head and neck. Am J Surg 1974; 128: 530–3PubMedCrossRefGoogle Scholar
  25. 25.
    Eilber FR, Morton DL, Ketcham AS. Immunologic abnormalities in head and neck cancer. Am J Surg 1974; 128: 534–8PubMedCrossRefGoogle Scholar
  26. 26.
    Wanebo HJ, Jun MY, Strong EW, et al. T-cell deficiency in patients with squamous cell cancer of the head and neck. Am J Surg 1975; 130: 445–51PubMedCrossRefGoogle Scholar
  27. 27.
    Hilal EY, Wanebo HJ, Pinsky CM, et al. Immunologic evaluation and prognosis in patients with head and neck cancer. Am J Surg 1977; 134: 469–73CrossRefGoogle Scholar
  28. 28.
    Meisel RH, Ogura JH. Dinitrochlorobenzene skin sensitivitation and peripheral lymphocyte count: predictors of survival in head and neck cancer. Ann Otol Rhinol Laryngol 1976; 85: 517–22Google Scholar
  29. 29.
    Gilbert HA, Kagan AR, Miles J, et al. The usefulness of pre-treatment DNCB in 85 patients with squamous cell carcinoma of the upper aerodigestive tract. J Surg Oncol 1978; 10: 73–7PubMedCrossRefGoogle Scholar
  30. 30.
    Zighelboim J, Dorey F, Parker NH, et al. Immunological evaluation of patients with advanced head and neck cancer receiving weekly chemoimmunotherapy. Cancer 1979; 44: 117–23PubMedCrossRefGoogle Scholar
  31. 31.
    Osaba D, Kersey PA, Clark RM, et al. Prognostic value of skin testing with dinitrochlorobenzene inpatients with head and neck cancer. Can J Surg 1980; 23: 43–8Google Scholar
  32. 32.
    Vasenwala SM, Aziz M, Rattan A, et al. Immunological status of patients in carcinoma head and neck. Indian J Cancer 1989; 26: 137–44PubMedGoogle Scholar
  33. 33.
    Bier J, Nicklisch U, Platz H. The doubtful relevance of nonspecific immune reactivity in patients with squamous cell carcinoma of the head and neck region. Cancer 1983; 52: 1165–72PubMedCrossRefGoogle Scholar
  34. 34.
    Olivari A, Pradier R, Feierstein J, et al. Cell-mediated immune response in head and neck cancer patients. J Surg Oncol 1976; 8: 287–94PubMedCrossRefGoogle Scholar
  35. 35.
    Brookes GB, Clifford P. Nutritional status and general immune competence in patients with head and neck cancer. J R Soc Med 1981; 74: 132–9PubMedGoogle Scholar
  36. 36.
    Good RA, Fernandez G, West A. Nutrition, immunity and cancer: a review. Part I: Influence of protein or protein-calorie malnutrition and zinc deficiency on immunity. Clin Bull 1979; 9: 3–12PubMedGoogle Scholar
  37. 37.
    Coto JA, Hadden EM, Sauro M, et al. Interleukin 1 regulates secretion of zinc-thymulin by human thymic epithelial cells and its action on T-lymphocyte proliferation and nuclear kinase C. Proc Natl Acad Sci USA 1992; 89: 7752–6PubMedCrossRefGoogle Scholar
  38. 38.
    Garofalo JA, Landson E, Strong EW, et al. Serum zinc, serum copper, and the Cu/Zn ratio in patients with epidermoid cancers of the head and neck. J Surg Oncol 1980; 15: 381–6PubMedCrossRefGoogle Scholar
  39. 39.
    Abdulla M, Biorklund A, Mathur A, et al. Zinc and copper levels in whole blood and plasma from patients with squamous cell carcinoma of head and neck. J Surg Oncol 1979; 12: 107–13PubMedCrossRefGoogle Scholar
  40. 40.
    Moccegiani E, Fabris N. In vivo and in vitro effect of zinc on thymic efficiency in old age [abstract]. Proceedings of the 4th International Congress of Biomedical Gerontology; 1991; Ancona, Italy: abstr. 197Google Scholar
  41. 41.
    Browder JP, Chretien PB. Immune reactivity in head and neck squamous cell carcinoma and relevance for the design of immunotherapy trials. Semin Oncol 1977; 4: 431–9PubMedGoogle Scholar
  42. 42.
    Schantz SP, Romsdahl MM, Babcock GF, et al. The effect of surgery on natural killer cell activity in head and neck cancer patients: in vitro reversal of a postoperatively suppressed immunosurveillance system. Laryngoscope 1985; 95: 588–94PubMedCrossRefGoogle Scholar
  43. 43.
    Tarpley JL, Potvin C, Chretien PB. Prolonged depression of cellular immunity in cured laryngopharyngeal cancer patients treated with radiation therapy. Cancer 1975; 35: 638–44PubMedCrossRefGoogle Scholar
  44. 44.
    Jenkins VK, Griffiths CM, Ray P, et al. Radiotherapy and head and neck cancer. Arch Otolaryngol Head Neck Surg 1980; 106: 414–8CrossRefGoogle Scholar
  45. 45.
    Gray WC, Chretien PB, Suter CM, et al. Effects of radiation therapy on T-lymphocyte subpopulations in patients with head and neck cancer. Arch Otolaryngol Head Neck Surg 1985; 93: 650–60Google Scholar
  46. 46.
    Wolf GT, Amendola BE, Diaz R, et al. Definite vs. adjuvant radiotherapy: comparative effects on lymphocyte subpopulations in patients with head and neck squamous carcinoma. Arch Otolaryngol Head Neck Surg 1985; 111: 716–25CrossRefGoogle Scholar
  47. 47.
    Deegan MJ, Coulthard SW, Qualman SJ, et al. A correlative analysis of in vitro parameters of cellular immunity in patients with squamous cell carcinoma of the head and neck. Cancer Res 1977; 37: 4475–81PubMedGoogle Scholar
  48. 48.
    Mason JM, Kitchens GG, Eastham RJ, et al. T-lymphocytes and survival of head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 1977; 103: 233–6CrossRefGoogle Scholar
  49. 49.
    Ryan RE, Neel HB III, Ritts RE. Correlation of preoperative immunologic test results with recurrence in patients with head and neck cancer. Arch Otolaryngol Head Neck Surg 1980; 88: 58–63Google Scholar
  50. 50.
    Papenhausen PR, Kukwa A, Croft CB, et al. Cellular immunity in patients with epidermoid cancer of the head and neck. Laryngoscope 1979; 89: 538–49PubMedCrossRefGoogle Scholar
  51. 51.
    Wolf GT, Lovett EJ, Peterson KA, et al. Lymphokine production and lymphocyte subpopulations in patients with head and neck squamous carcinoma. Arch Otolaryngol Head Neck Surg 1984; 110: 731–5CrossRefGoogle Scholar
  52. 52.
    Balaram P, Vasudevan DM. Quantitation of Fc receptor-bearing T-lymphocytes (TG and TM) in oral cancer. Cancer 1983; 52: 1837–40PubMedCrossRefGoogle Scholar
  53. 53.
    Johnson JT, Rabin BS, Hirsch B, et al. T-cell subpopulations in head and neck carcinoma. Arch Otolaryngol Head Neck Surg 1984; 92: 381–5Google Scholar
  54. 54.
    Dawson DE, Everts EC, Vetto RM, et al. Assessment of immunocompetent cells in patients with head and neck squamous cell carcinoma. Ann Otol Rhinol Laryngol 1985; 94: 342–5PubMedGoogle Scholar
  55. 55.
    Schuller DE, Rock RP, Rinehart JJ, et al. T-lymphocytes as a prognostic indicator in head and neck cancer. Arch Otolaryngol Head Neck Surg 1986; 112: 938–42PubMedCrossRefGoogle Scholar
  56. 56.
    Strome M, Clark JR, Fried MP, et al. T-cell subsets and natural killer cell function with squamous cell carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg 1987; 113: 1090–3PubMedCrossRefGoogle Scholar
  57. 57.
    Wolf GT, Schmaltz S, Hudson J, et al. Alterations in T-lymphocyte subpopulations in patients with head and neck cancer. Arch Otolaryngol Head Neck Surg 1987; 113: 1200–6PubMedCrossRefGoogle Scholar
  58. 58.
    Schantz SP, Liu FJ. An immunologic profile of young adults with head and neck cancer. Cancer 1989; 64: 1232–7PubMedCrossRefGoogle Scholar
  59. 59.
    Eskinazi DP, Helman J, Ershow AG, et al. Nonspecific immunity and head and neck cancer: blastogenesis reviewed and revisited. Oral Surg Oral Med Oral Pathol 1985; 60: 642–7PubMedCrossRefGoogle Scholar
  60. 60.
    Eskinazi DP, Perna JJ, Ershow AG, et al. Depressed PMNC blastogenic response in patients with cancer of the head and neck: a study of IL-2 production, IL-2 consumption, and IL-2 receptor expression. Laryngoscope 1989; 99: 151–7PubMedCrossRefGoogle Scholar
  61. 61.
    Veltri RW, Rodman SM, Maxim PE. Immune complexes, serum proteins, cell-mediated immunity and immune regulation in patients with squamous cell carcinoma of the head and neck. Cancer 1986; 57: 2295–9PubMedCrossRefGoogle Scholar
  62. 62.
    Wanebo HJ, Jones T, Pace R, et al. Immune restoration with interleukin-2 in patients with squamous cell carcinoma of the head and neck. Am J Surg 1989; 158: 356–60PubMedCrossRefGoogle Scholar
  63. 63.
    Yamanaka N, Harabuchi Y, Himi T, et al. Immunosuppressive substances in the sera of head and neck cancer patients. Cancer 1988; 62: 1293–8PubMedCrossRefGoogle Scholar
  64. 64.
    Bugis SP, Lotzova E, Savage HE, et al. Inhibition of lymphokine-activated killer cell generation by blocking in sera of patients with head and neck cancer. Cancer Immunol Immunother 1990; 31: 176–81PubMedCrossRefGoogle Scholar
  65. 65.
    Clayman GL, Young G, Tayler DL, et al. Detection of regulatory factors of lymphokine-activated killer cell activity in head and neck cancer patients treated with interleukin-2 and interferon alpha. Ann Otol Rhinol Laryngol 1992; 101: 909–15PubMedGoogle Scholar
  66. 66.
    Wanebo HJ, Blackington D, Kouttab N, et al. Contribution of serum inhibitory factors and immune cellular defects to the depressed cell-mediated immunity in patients with head and neck cancer. Am J Surg 1993; 166: 389–94PubMedCrossRefGoogle Scholar
  67. 67.
    Jacobs D, Houri M, Landon J, et al. Circulating levels of immunoglobulin E in patients with cancer. Lancet 1972; 2: 1059–64PubMedCrossRefGoogle Scholar
  68. 68.
    Brown AM, Lally ET, Frankel A, et al. The association of the IgA levels of serum and whole saliva with the progression of oral cancer. Cancer 1975; 35: 1154–62PubMedCrossRefGoogle Scholar
  69. 69.
    Katz AE, Nysather JO, Harker LE. Major immunoglobulin ratios in carcinoma of the head and neck. Ann Otol Rhinol Laryngol 1978; 87: 412–5PubMedGoogle Scholar
  70. 70.
    Baskies AM, Chretien PB, Maxim PE, et al. Circulating immune complexes correlate with levels of serum immune reactive proteins and clinical tumor stage in head and neck squamous carcinoma. Surg For 1980; 31: 526–7Google Scholar
  71. 71.
    Khanna NN, Das SN, Khanna S. Serum immunoglobulins in squamous cell carcinoma of the oral cavity. J Surg Oncol 1982; 20: 46–8PubMedCrossRefGoogle Scholar
  72. 72.
    Schantz SP, Liu FJ, Taylor D, et al. The relationship of circulating IgA to cellular immunity in head and neck cancer patients. Laryngoscope 1988; 98: 671–8PubMedCrossRefGoogle Scholar
  73. 73.
    Lal H, Singh B, Wig U, et al. Serum immunoglobulin E levels in patients with head and neck cancer. J Laryngol Otol 1988; 102: 432–7PubMedCrossRefGoogle Scholar
  74. 74.
    Baskies AM, Chretien PB, Yang C-S, et al. Serum glycoproteins and immunoglobulins in nasopharyngeal carcinoma. Am J Surg 1989; 138: 478–88CrossRefGoogle Scholar
  75. 75.
    Veltri RW, Rodman SM, Maxim PE, et al. Immune complexes, serum proteins, cell-mediated immunity, and immune regulation in patients with squamous cell carcinoma of the head and neck. Cancer 1986; 57: 2295–308PubMedCrossRefGoogle Scholar
  76. 76.
    Katz AE. Immunobiologic staging of patients with carcinoma of the head and neck. Laryngoscope 1983; 93: 445–63PubMedGoogle Scholar
  77. 77.
    Baseler MW, Maxim PE, Veltri RW. Circulating IgA immune complexes in head and neck cancer, nasopharyngeal carcinoma, lung cancer, and colon cancer. Cancer 1987; 59: 1727–31PubMedCrossRefGoogle Scholar
  78. 78.
    Susal C, Maier H, Lorenz K, Opelz G. Association of IgA-Fab autoantibodies with disease stage in head and neck cancer. Int J Cancer 1994; 57(1): 47–50PubMedCrossRefGoogle Scholar
  79. 79.
    Hargett S, Wanebo HJ, Pace R, et al. Interleukin-2 production in head and neck cancer patients. Am J Surg 1985; 150: 456–60PubMedCrossRefGoogle Scholar
  80. 80.
    Wolf GT, Hudson J, Peterson KA, et al. Interleukin-2 receptor expression in patients with head and neck squamous carcinoma: effects of thymosin α1 in vitro. Arch Otolaryngol Head Neck Surg 1989; 115: 1345–9PubMedCrossRefGoogle Scholar
  81. 81.
    Wustrow TPU, Kabelitz D. Interleukin-2 release from lymphocytes of patients with head and neck cancer. Ann Otol Rhinol Laryngol 1989; 98: 179–84PubMedGoogle Scholar
  82. 82.
    Pierri I, Rogna S, Garaventa G, et al. Decreased sensitivity of T lymphocytes to normal adherent suppressor cells in patients with head and neck cancer. Cancer Detect Prev 1984; 7: 73–8PubMedGoogle Scholar
  83. 83.
    Wolf GT, Peterson KA, Lovett III EJ. In vitro immune modulation by thymosin alpha1 in patients with head and neck squamous cell carcinoma. Head Neck Surg 1985; 7: 350–6PubMedCrossRefGoogle Scholar
  84. 84.
    Yamanaka N. Immunomodulatory serum components in head and neck cancer. Eur J Cancer 1993; 29B(2): 103–6Google Scholar
  85. 85.
    Berlinger NT, Hilal EY, Oettgen HF, et al. Deficient cell-mediated immunity in head and neck cancer patients secondary to autologous suppressive immune cells. Laryngoscope 1978; 88: 470–82PubMedCrossRefGoogle Scholar
  86. 86.
    Goodwin JS, Ceuppens J. Regulation of the immune response by prostaglandins. J Clin Immunol 1983; 3: 295–315PubMedCrossRefGoogle Scholar
  87. 87.
    Balch CM, Dougherty PA, Tilden A. Excessive prostaglandin E2 production by suppressor monocytes in head and neck cancer patients. Ann Surg 1982; 196: 645–50PubMedCrossRefGoogle Scholar
  88. 88.
    Berlinger NT. Deficient immunity in head and neck cancer due to excessive monocyte production of prostaglandins. Laryngoscope 1984; 94: 1407–10PubMedCrossRefGoogle Scholar
  89. 89.
    McCormick KJ, Panje WR. Indomethacin-induced augmentation of lymphoproliferative responses in patients with head and neck cancer. Cancer Immunol Immunother 1986; 21: 226–32PubMedCrossRefGoogle Scholar
  90. 90.
    Hirsch B, Johnson JT, Rabin BS, et al. Immunostimulation of patients with head and neck cancer: in vitro and preliminary clinical experiences. Arch Otolaryngol 1983; 109: 298–301PubMedCrossRefGoogle Scholar
  91. 91.
    Maca RD, Panje WR. Indomethacin-sensitive suppressor cell activity in head and neck cancer patients pre-and post-irradiation therapy. Cancer 1982; 50: 483–9PubMedCrossRefGoogle Scholar
  92. 92.
    Garraud O, Faucher A, Legrand E. Impairment of monocyte functions in advanced head and neck cancer. Immunol Lett 1988; 18: 213–8PubMedCrossRefGoogle Scholar
  93. 93.
    Balm FJ, Drexhage HA, von Blumberg ME, et al. Mononuclear phagocyte function in head and neck cancer: NBT-dye reduction, maturation and migration of peripheral blood monocytes. Laryngoscope 1982; 92: 810–4PubMedCrossRefGoogle Scholar
  94. 94.
    Balm FAJM, Drexhage HA, von Blomberg M, et al. Mononuclear phagocyte function in head and neck cancer. Cancer 1984; 54: 1010–5PubMedCrossRefGoogle Scholar
  95. 95.
    Balm FJM, von Blomberg-van DeFlier BME, Drexhage HA, et al. Mononuclear phagocyte function in head and neck cancer: depression of murine macrophage accumulation by low molecular weight factors derived from head and neck carcinomas. Laryngoscope 1984; 94: 223–7PubMedCrossRefGoogle Scholar
  96. 96.
    Walter RJ, Danielson JR. Defective monocyte chemotaxis in patients with epidermoid tumors of the head and neck. Arch Otolaryngol Head Neck Surg 1985; 111: 538–40CrossRefGoogle Scholar
  97. 97.
    Tan IB, Drexhage HA, Scheper RJ, et al. Defective monocyte chemotaxis in patients with head and neck cancer. Arch Otolaryngol Head Neck Surg 1986; 112: 541–4PubMedCrossRefGoogle Scholar
  98. 98.
    Tas MPR, Simons PJ, Balm FJM, et al. Depressed monocyte polarization and clustering of dendritic cells in patients with head and neck cancer: in vitro restoration of this immunosuppression by thymic hormones. Cancer Immunol Immunother 1993; 36: 108–14PubMedCrossRefGoogle Scholar
  99. 99.
    Cameron DJ, Stromberg BV. The ability of macrophages from head and neck cancer patients to kill tumor cells. Cancer 1984; 54: 2403–8PubMedCrossRefGoogle Scholar
  100. 100.
    Simons PJ, Oostendorp RA, Tas MP, et al. Comparison of retroviral p15E-related factors and interferon alpha in head and neck cancer. Cancer Immunol Immunother 1994: 38(3): 178–84PubMedGoogle Scholar
  101. 101.
    Hadden JW, Endicott J, Baekey P, et al. Interleukins and contrasuppression induce immune regression of head and neck cancer. Arch Otolaryngol Head Neck Surg 1994; 120: 395–403PubMedCrossRefGoogle Scholar
  102. 102.
    Sato M, Yoshida H, Yanagawa T, et al. Interferon activity and its characterization in the sera of patients with head and neck cancer. Cancer 1984; 54: 1239–51PubMedCrossRefGoogle Scholar
  103. 103.
    Schantz S, Poisson L, Romsdahl MM, et al. Natural killer cell activity and head and neck cancer. Proc Am Assoc Cancer Res 1985; 26: 308Google Scholar
  104. 104.
    Schantz SP, Shilltoe EJ, Brown B, et al. Natural killer cell activity and head and neck cancer: a clinical assessment. J Natl Cancer Inst 1986; 77: 869–75PubMedGoogle Scholar
  105. 105.
    Eskinazi DP, Perna JJ, Mihail R. Mononuclear cell subsets in patients with oral cancer. Cancer 1987; 60: 376–81PubMedCrossRefGoogle Scholar
  106. 106.
    Wustrow TPU, Zenner H-P. Natural killer cell activity in patients with carcinoma of the larynx and hypopharynx. Laryngoscope 1985; 95: 1391–400PubMedCrossRefGoogle Scholar
  107. 107.
    Luger TA, Uchida A, Kock A, et al. Human epidermal cells and squamous carcinoma cells synthesize a cytokine that augments natural killer cell activity. J Immunol 1985; 134: 2477–83PubMedGoogle Scholar
  108. 108.
    Beauchamp ML, Wolf GT. Monocytes and impaired leukocyte migration inhibitory factor production in head and neck squamous carcinoma. Head Neck Surg 1988; 10: 187–94PubMedCrossRefGoogle Scholar
  109. 109.
    Hanna EYN, Papay FA, Gupta MK, et al. Serum tumor markers of head and neck cancer: current status. Head Neck Surg 1990; 12: 50–9CrossRefGoogle Scholar
  110. 110.
    Palermo F, Carniato A, Fede A, et al. Serum SCC-Ag in head and neck squamous cell carcinoma. Int J Biol Markers 1990; 5: 118–20PubMedGoogle Scholar
  111. 111.
    Fishbach W, Meyer T, Barthel K. Squamous cell carcinoma antigen in the diagnosis and treatment follow-up of oral and facial squamous cell carcinoma. Cancer 1990; 65: 1321–4CrossRefGoogle Scholar
  112. 112.
    Henle W, Ho H-C, Henle G, et al. Antibodies to Epstein-Barr virus-related antigens in nasopharyngeal carcinoma: comparison to active cases with long-term survivors. J Natl Cancer Inst 1973; 51: 361–9PubMedGoogle Scholar
  113. 113.
    Sako K, Minowada J, Marchetta FC. Epstein-Barr virus antibodies in patients with carcinoma of the nasopharynx and carcinoma of other sites in the head and neck. Am J Surg 1975; 130: 437–9PubMedCrossRefGoogle Scholar
  114. 114.
    Henle G, Henle W. Epstein-Barr virus-specific IgA serum antibodies as an outstanding feature of nasopharyngeal carcinoma. Int J Cancer 1976; 17: 1–7PubMedCrossRefGoogle Scholar
  115. 115.
    Tosato G, Magrath I, Koski I, et al. Activation of suppressor T cells during Epstein-Barr-virus-induced infectious mononucleosis. N Engl J Med 1979; 301: 1133–7PubMedCrossRefGoogle Scholar
  116. 116.
    Sundar SK, Ablashi DV, Kamaraju LS, et al. Sera from patients with undifferentiated nasopharyngeal carcinoma contain a factor which abrogates specific Epstein-Barr virus antigen-induced lymphocyte response. Int J Cancer 1982; 29: 407–12PubMedCrossRefGoogle Scholar
  117. 117.
    Hollingshead AC, Lee O, Chretien PB, et al. Antibodies to herpesvirus nonviron antigens in squamous carcinomas. Science 1973; 182: 713–5CrossRefGoogle Scholar
  118. 118.
    Silverman NA, Alexander JC, Hollingshead AC, et al. Correlation of tumor burden with in vitro lymphocyte reactivity and antibodies to herpesvirus tumor-associated antigens in head and neck squamous carcinoma. Cancer 1976; 37: 135–40PubMedCrossRefGoogle Scholar
  119. 119.
    Smith HG, Chretien PB, Henson DE, et al. Viral-specific humoral immunity to herpes simplex-induced antigens in patients with squamous carcinoma of the head and neck. Am J Surg 1976; 132: S41–S48CrossRefGoogle Scholar
  120. 120.
    Field JK. Oncogenes and tumour-suppressor genes in squamous cell carcinoma of the head and neck. Oral Oncol Eur J Cancer 1992; 28B: 67–76CrossRefGoogle Scholar
  121. 121.
    Popovic D, Gill L, Sisson G, et al. Detection and localization of tumor-associated immune components of head and neck squamous cell carcinomas. Trans Am Acad Opthalmol Otolaryngol 1976; 82: 119–30Google Scholar
  122. 122.
    Sofen H, OαToole C. Anti-squamous tumor antibodies in patients with squamous cell carcinoma. Cancer Res 1978; 36: 199–203Google Scholar
  123. 123.
    Krajina Z, Bura M, Bolanca S. Implication of tumour antigens and immune complexes in laryngeal cancer. Acta Otolaryngol 1991; 111: 434–6PubMedCrossRefGoogle Scholar
  124. 124.
    Vlock DR, Arnold B, Humpierres J, et al. Serial studies of autologous antibody reactivity to squamous cell carcinoma of the head and neck. Cancer Immunol Immunother 1992; 34: 329–36PubMedCrossRefGoogle Scholar
  125. 125.
    Berlinger NT, Tsakraklides V, Pollak K, et al. Immunologic assessment of regional lymph node histology in relation to survival in head and neck carcinoma. Cancer 1976; 37: 697–705PubMedCrossRefGoogle Scholar
  126. 126.
    Berlinger NT, Tsakraklides V, Pollak K, et al. Prognostic significance of lymph node histology in patients with squamous cell carcinoma of the larynx, pharynx, or oral cavity. Laryngoscope 1976: 86: 792–803PubMedCrossRefGoogle Scholar
  127. 127.
    Ring AH, Sako K, Rao U, et al. Immunologic patterns of regional lymph nodes in squamous cell carcinoma of the floor of the mouth: prognostic significance. Am J Surg 1985; 150: 461–5PubMedCrossRefGoogle Scholar
  128. 128.
    Ferlito A, Polidoro F. Biological and prognostic implications of the morphologic aspects of immune reaction in lymph nodes draining head and neck cancers. J Laryngol Otol 1979; 93: 153–75PubMedCrossRefGoogle Scholar
  129. 129.
    Roubin R, Bekkoucha F, Fondaneche M-C, et al. Lymphoid cells in lymph nodes and peripheral blood of patients with squamous cell carcinoma of the head and neck. J Cancer Res Clin Oncol 1982; 102: 277–87PubMedCrossRefGoogle Scholar
  130. 130.
    Schuller DE, Rock RP, Rinehart JJ, et al. T-lymphocytes as a prognostic indicator in head and neck cancer. Arch Otolaryngol Head Neck Surg 1986; 112: 938–41PubMedCrossRefGoogle Scholar
  131. 131.
    Snyderman CH, Heo DS, Johnson JT, et al. Functional and phenotypic analysis of lymphocytes in head and neck cancer. Arch Otolaryngol Head Neck Surg 1991; 117: 899–905PubMedCrossRefGoogle Scholar
  132. 132.
    Vinzenz K, Micksche M. Natural cytotoxicity in draining lymph nodes of squamous cell cancer in the maxillofacial region. J Oral Maxillofac Surg 1987; 45: 42–7PubMedCrossRefGoogle Scholar
  133. 133.
    Cozzolino F, Torcia M, Carossino AM, et al. Characterization of cells from invaded lymph nodes in patients with solid tumors: lymphokine requirement for tumor-specific lymphoid proliferative response. J Exp Med 1987; 166: 303–18PubMedCrossRefGoogle Scholar
  134. 134.
    Kessler DJ, Mickel RA, Lichtenstein A. Depressed natural killer cell activity in cervical lymph nodes containing focal metastatic squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 1988; 114: 313–8PubMedCrossRefGoogle Scholar
  135. 135.
    Eura M, Maehara T, Ikawa T, et al. Suppressor cells in the effector phase of autologous cytotoxic reactions in cancer patients. Cancer Immunol Immunother 1988; 27: 147–53PubMedCrossRefGoogle Scholar
  136. 136.
    Letessier EM, Sacchi M, Johnson JT, et al. The absence of lymphoid suppressor cells in tumor-involved lymph nodes of patients with head and neck cancer. Cell Immunol 1990; 130: 446–58PubMedCrossRefGoogle Scholar
  137. 137.
    Letessier EM, Heo DS, Okarama T, et al. Enrichment in tumor-reactive CD8+ T-lymphocytes by positive selection from the blood and lymph nodes of patients with head and neck cancer. Cancer Res 1991; 51: 3891–9PubMedGoogle Scholar
  138. 138.
    Bennett SH, Futrell JW, Roth JA, et al. Prognostic significance of histologic host response in cancer of the larynx or hypopharynx. Cancer 1971; 28: 1255–65PubMedCrossRefGoogle Scholar
  139. 139.
    Paavolainen M, Tarkkanen J, Saksela E. Stromal reactions as prognostic factors in epidermal carcinoma of the tongue. Acta Otolaryngol 1973; 75: 316–7PubMedCrossRefGoogle Scholar
  140. 140.
    Koneval T, Applebaum E, Popovic D, et al. Demonstration of immunoglobulin in tumor and marginal tissues of squamous cell carcinomas of the head and neck. J Natl Cancer Inst 1977; 59: 1089–93PubMedGoogle Scholar
  141. 141.
    Hiratsuka H, Imamura M, Kasai K. Lymphocyte subpopulations and T-cell subsets in human oral cancer tissues: immunohistologic analysis by monoclonal antibodies. Am J Clin Pathol 1984; 81: 464–70PubMedGoogle Scholar
  142. 142.
    Hiratsuka H, Imamura M, Ishii Y, et al. Immunohistologic detection of lymphocyte subpopulations infiltrating in human oral cancer with special reference to its clinical significance. Cancer 1984; 53: 2456–66PubMedCrossRefGoogle Scholar
  143. 143.
    Broemal TL, Becker WM, Otto HF. Identification of inflammatory cell phenotypes in human oral carcinomas by means of monoclonal antibodies. Arch Oral Biol 1983; 28: 1093–100CrossRefGoogle Scholar
  144. 144.
    Wolf GT, Hudson JL, Peterson KA, et al. Lymphocyte subpopulations infiltrating squamous carcinomas of the head and neck: correlations with extent of tumor and prognosis. Arch Otolaryngol Head Neck Surg 1986; 95: 142–52Google Scholar
  145. 145.
    Guo M, Rabin BS, Johnson JT, et al. Lymphocyte phenotypes at tumor margins in patients with head and neck cancer. Head Neck Surg 1987; 9: 265–71PubMedCrossRefGoogle Scholar
  146. 146.
    Danielson JR, Franklin WA. Characterization of antibody-forming cells adjacent to laryngeal carcinoma. Arch Otolaryngol Head Neck Surg 1984; 110: 327–8CrossRefGoogle Scholar
  147. 147.
    Rabin BS, Johnson JT, Claassen D. Identification of subsets of lymphocytes infiltrating head and neck tumor tissue: a preliminary report. Laryngoscope 1984; 94: 688–90PubMedCrossRefGoogle Scholar
  148. 148.
    Zeromski J, Szmeja Z, Rewers A, et al. Immunofluorescent assessment of tumour infiltrating cells in laryngeal carcinoma. Acta Otolaryngol 1986; 102: 325–32PubMedCrossRefGoogle Scholar
  149. 149.
    Nomori H, Watanabe S, Nakajima T, et al. Histiocytes in nasopharyngeal carcinoma in relation to prognosis. Cancer 1986; 57: 100–5PubMedCrossRefGoogle Scholar
  150. 150.
    Boheim K, Denz H, Boheim C, et al. An immunohistologic study of the distribution and status of activation of head and neck tumor infiltrating leukocytes. Arch Otorhinolaryngol 1987; 244: 127–32PubMedCrossRefGoogle Scholar
  151. 151.
    Neuchrist C, Grasl M, Schneider O, et al. Squamous cell carcinoma: infiltrating monocyte/macrophage subpopulations express functional mature phenotype. Br J Cancer 1990; 62: 748–53PubMedCrossRefGoogle Scholar
  152. 152.
    Horst H-A, Horny H-P. Tumor-infiltrating lymphoreticular cells. Histologic and immunohistologic investigations performed on metastasizing squamous cell carcinomas of the head and neck. Cancer 1991; 68: 2397–402PubMedCrossRefGoogle Scholar
  153. 153.
    Horiuchi K, Mishima K, Ohsawa M, et al. Prognostic factors for well-differentiated squamous cell carcinoma in the oral cavity with emphasis on immunohistochemical evaluation. J Surg Oncol 1993; 53: 92–6PubMedCrossRefGoogle Scholar
  154. 154.
    Heo DS, Whiteside TL, Johnson JT, et al. Long-term interleukin 2-dependent growth and cytotoxic activity of tumor-infiltrating lymphocytes from human squamous cell carcinomas of the head and neck. Cancer Res 1987; 47: 6353–62PubMedGoogle Scholar
  155. 155.
    Boscia R, Johnson JT, Chen K, et al. Evaluation of therapeutic potential of interleukin 2-expanded tumor-infiltrating lymphocytes in squamous cell carcinoma of the head and neck. Ann Otol Rhinol Laryngol 1988; 97: 414–21PubMedGoogle Scholar
  156. 156.
    Tatake RJ, Krishnan N, Rao RS, et al. Lymphokine-activated killer-cell function of lymphocytes from peripheral blood, regional lymph nodes and tumor tissues of patients with oral cancer. Int J Cancer 1989; 43: 560–6PubMedCrossRefGoogle Scholar
  157. 157.
    Murali PS, Somasundaram R, Rao RS, et al. Interleukin-2 mediated regulation of mitogen-activated T cell reactivity from different lymphoid sources in patients with squamous cell carcinoma of the oral cavity. J Oral Pathol Med 1989; 18: 327–32PubMedCrossRefGoogle Scholar
  158. 158.
    Leess RF, Bredenkamp JK, Lichtenstein A, et al. Lymphokine-activated killing of autologous and allogenic short-term cultured head and neck carcinomas. Laryngoscope 1989; 99: 1255–61PubMedCrossRefGoogle Scholar
  159. 159.
    Ortega IS, Nieto CS, Forcelledo MFF, et al. Lymph node response and its relationship to prognosis in carcinomas of the head and neck. Clin Otolaryngol 1987; 12: 241–7CrossRefGoogle Scholar
  160. 160.
    Yasumura S, Weidmann E, Hirabayashi H, et al. HLA restriction and T-cell-receptor V beta gene expression of cytotoxic T lymphocytes reactive with human squamous-cell carcinoma of the head and beck. Int J Cancer 1994; 57(3): 297–305PubMedCrossRefGoogle Scholar
  161. 161.
    Vitolo D, Letessier EM, Johnson JT, et al. Immunologic effector cells in head and neck cancer. Monogr Natl Cancer Inst 1992; 12: 203–8Google Scholar
  162. 162.
    Vitolo D, Kanbour A, Johnson JT, et al. In situ hybridisation for cytokine gene transcripts in the solid tumor microenvironment. Eur J Cancer 1993; 29: 371–7CrossRefGoogle Scholar
  163. 163.
    Tsukuda M, Mochimatsu I, Sakumoto M, et al. Autologous tumor cell killing activity of tumor-associated lymphocytes in patients with head and neck carcinomas. Biotherapy 1993; 6: 155–61PubMedCrossRefGoogle Scholar
  164. 164.
    Yasamura S, Hirabayashi H, Schwartz DR, et al. Human cytotoxic T-cell lines with restricted specificity for squamous cell carcinoma of the head and neck. Cancer Res 1993; 53: 1461–8Google Scholar
  165. 165.
    Chikamatsu K, Eura M, Matsuoka H, et al. The role of major histocompatibility complex expression on head and neck cancer cells in the induction of autologous cytotoxic T lymphocytes. Cancer Immunol Immunother 1994; 38(6): 358–64PubMedCrossRefGoogle Scholar
  166. 166.
    Jerome KR, Barnd DL, Bendt KM, et al. Cytotoxic T-lymphocytes derived from patients with breast adenocarcinoma recognize an epitope present on the protein core of a mucin molecule preferentially expressed by malignant cells. Cancer Res 1991; 51: 2908–16PubMedGoogle Scholar
  167. 167.
    Jerome KR, Domenech N, Finn OJ. Tumor-specific cytotoxic T cell clones from patients with breast and pancreatic adenocarcinoma recognize EBV-immortalized B cells transfected with polymorphic epithelial mucin complementary DNA. J Immunol 1993; 151: 1654–62PubMedGoogle Scholar
  168. 168.
    Lin F, Liu PI, McGregor DH. Isoantigens A, B, and H in morphologically normal mucosa and in carcinoma of the larynx. Am J Clin Pathol 1977; 68: 372–6PubMedGoogle Scholar
  169. 169.
    Byrne M, Thrane PS, Dabelsteen E. Loss of expression of blood group antigen H is associated with cellular invasion and spread of oral squamous cell carcinomas. Cancer 1991; 67: 613–8CrossRefGoogle Scholar
  170. 170.
    Houck JR, Sexton FM, Zajdel G. HLA class I and class II antigen expression on squamous cell carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg 1990; 116: 1181–5PubMedCrossRefGoogle Scholar
  171. 171.
    Estaban F, Concha A, Delgado M, et al. Lack of MHC class I antigens and tumour aggressiveness of the squamous cell carcinoma of the larynx. Br J Cancer 1991; 62: 1047–51CrossRefGoogle Scholar
  172. 172.
    Estaban F, Ruiz-Cabello F, Concha A, et al. HLA-DR expression is associated with excellent prognosis in squamous cell carcinoma of the larynx. Clin Exp Metastasis 1990; 8: 319–28CrossRefGoogle Scholar
  173. 173.
    Mutlu S, Scully C, Prime SS. Effect of IFN-gamma on the expression of MHC class I and II antigens in a human malignant oral epithelial cell line. J Oral Pathol Med 1991; 20: 218–21PubMedCrossRefGoogle Scholar
  174. 174.
    Richtsmeier WJ. Interferon gamma induced oncolysis: an effect on head and neck squamous carcinoma cultures. Arch Otolaryngol Head Neck Surg 1988; 114: 432–7PubMedCrossRefGoogle Scholar
  175. 175.
    Becciolini A, Porciani S, Lanini A, et al. Prognostic significance of tissue polypeptide antigen (TPA) in head and neck carcinomas. Acta Otolaryngol 1993; 32: 295–9Google Scholar
  176. 176.
    Molina R, Moragas M, Perez-Villa J, et al. TPS and SCC antigens in serum of patients with head and neck cancer: preliminary results. J Tumor Oncol 1992; 7: 60Google Scholar
  177. 177.
    Pectasides D, Bourazanis J, Economides N, et al. Squamous cell carcinoma antigen (SCC), carcinoembryonic antigen (CEA), and tumour-associated trypsin inhibitor (TATI) for monitoring head and neck cancer. Int J Biol Markers 1993; 8(2): 81–7PubMedGoogle Scholar
  178. 178.
    Straka MB, Wagner RL, Johnson JT, et al. The lack of utility of a tumor marker panel in head and neck carcinoma. Squamous cell carcinoma antigen, carcinoembryonic antigen, lipid-associated sialic acid, and CA-125. Arch Ontolaryngol 1992; 118(8): 802–5CrossRefGoogle Scholar
  179. 179.
    Saccani J, Fontanesi M, Columbo A, et al. Localization of mucinous-like carcinoma associated antigen (MCA) in breast pathology: comparison with carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA). Int J Biol Markers 1990; 5: 145–52Google Scholar
  180. 180.
    Kantor J, Irvine K, Abrams S, et al. Antitumor activity and immune responses induced by a recombinant carcinoembryonic antigen-vaccinia virus vaccine. J Natl Cancer Inst 1992; 84: 1084–91PubMedCrossRefGoogle Scholar
  181. 181.
    Kearsley JH, Stenzel DJ, Sculley TB, et al. Cellular localisation of tumour antigen (TA-4) in normal, dysplastic and neoplastic squamous epithelia of the upper aerodigestive tract. Br J Cancer 1990; 61: 631–5PubMedCrossRefGoogle Scholar
  182. 182.
    Springer G. T and Tn, general carcinoma autoantigens. Science 1984; 224: 1198–206Google Scholar
  183. 183.
    Xing PI, Tjandra JJ, Stacker SA, et al. Monoclonal antibodies reactive with mucin expressed in breast cancer. Immunol Cell Biol 1989; 67: 183–95PubMedCrossRefGoogle Scholar
  184. 184.
    Layton GT, Devine PL, Warren JA, et al. Monoclonal antibodies reactive with the breast carcinoma-associated mucin core protein repeat sequence peptide also recognise the ovarian carcinoma-associated sebaceous gland antigen. Tumor Biol 1990; 11: 274–86CrossRefGoogle Scholar
  185. 185.
    Ding L, Lalani E-N, Reddish M, et al. Immunogenicity of synthetic peptides related to the core peptide sequence encoded by the human MUC1 mucin gene: effect of immunization on the growth of murine mammary adenocarcinoma cells transfected with the human MUC1 gene. Cancer Immunol Immunother 1993; 36: 9–17PubMedCrossRefGoogle Scholar
  186. 186.
    Singhal A, Fohn M, Hakomori S-I. Induction of α-N-acetylgalactosamine-O-serine/threonine (Tn) antigen-mediated cellular immune response for active immunotherapy in mice. Cancer Res 1991; 51: 1406–11PubMedGoogle Scholar
  187. 187.
    MacLean GD, Reddish M, Koganty RR, et al. Immunization of breast cancer patients using a synthetic sialyl-Tn glyco-conjugate plus Detox adjuvant. Cancer Immunol Immunother 1993; 36: 215–22PubMedCrossRefGoogle Scholar
  188. 188.
    MacLean GD, Longenecker BM. Prospects for an immunological approach to therapy of ovarian cancer. Clin Immunother 1994; 2(6): 409–414CrossRefGoogle Scholar
  189. 189.
    Crawford V, Pim DC, Bulbrook RD. Detection of antibodies against the cellular protein p53 in sera from patients with breast cancer. Int J Cancer 1982; 30: 403–8PubMedCrossRefGoogle Scholar
  190. 190.
    Schlichtholz B, Legros Y, Gillet D, et al. The immune response to p53 in breast cancer patients is directed against immunodominant epitopes unrelated to the mutational hot spot. Cancer Res 1992; 52: 6380–4PubMedGoogle Scholar
  191. 191.
    Isola I, Visakorpi T, Holli N, et al. Association of overexpression of tumor suppression protein p53 with rapid cell proliferation and poor prognosis in node-negative breast cancer patients. J Natl Cancer Inst 1992; 84: 1109–14PubMedCrossRefGoogle Scholar
  192. 192.
    Fendly BM, Knotts C, Vetterlein D, et al. The extracellular domain of HER2/neu is a potential immunogen for active specific immunotherapy of breast cancer. J Biol Response Mod 1990; 9: 449–55PubMedGoogle Scholar
  193. 193.
    Wels W, Harwert IM, Mueller M, et al. Selective inhibition of tumor cell growth by a recombinant single-chain antibody-toxin specific for the Erb-2 receptor. Cancer Res 1992; 52: 6310–7PubMedGoogle Scholar
  194. 194.
    Friedman PN, Chace DF, Trail PA, et al. Antitumor activity of the single-chain immunotoxin BR96 sFv-PE40 against established breast and lung tumor xenografts. J Immunol 1993; 150: 3054–61PubMedGoogle Scholar
  195. 195.
    Kimmel KA, Carey TE. Altered expression in squamous carcinoma cells of an orientation restricted epithelial antigen directed by monoclonal antibody AP1. Cancer Res 1986; 46: 3614–23PubMedGoogle Scholar
  196. 196.
    Wolf GT, Carey TE, Schmaltz SP, et al. Altered antigen expression predicts outcome in squamous cell carcinoma of the head and neck. J Natl Cancer Inst 1990; 82: 1566–72PubMedCrossRefGoogle Scholar
  197. 197.
    Van Waes C, Kozarsky KF, Warren AB, et al. The A9 antigen associated with aggressive human squamous carcinoma is structurally and functionally similar to the newly defined integrin α6 β41. Cancer Res 1991; 51: 2395–402PubMedGoogle Scholar
  198. 198.
    Van Waes C, Carey TE. Overexpression of the A9 antigen/α6β4 integrin in head and neck cancer. Mol Biol Genet 1992; 25: 1117–38Google Scholar
  199. 199.
    Jones J, Sugiyama M, Watt FM, et al. Integrin expression in normal, hyperplastic, dysplastic, and malignant oral epithelium. J Pathol 1993; 169: 235–43PubMedCrossRefGoogle Scholar
  200. 200.
    Salmi M, Gron-Virta K, Sointu P, et al. Regulated expression of EXON V6 containing isoforms of CD44 in man: down-regulation during malignant transformation of tumors of squamocellular origin. J Cell Biol 1993; 122: 431–42PubMedCrossRefGoogle Scholar
  201. 201.
    Harada H, Osaki Y, Kukita T, et al. Monoclonal antibody G6K12 specific for membrane-associated differentiation marker of human stratified squamous epithelia and squamous cell carcinoma. J Oral Pathol Med 1993; 22: 145–52PubMedCrossRefGoogle Scholar
  202. 202.
    Eibling DE, Johnson JT, Wagner RL, et al. SCC-RIA in the diagnosis of squamous cell carcinoma of the head and neck. Laryngoscope 1989; 99(2): 117–24PubMedCrossRefGoogle Scholar
  203. 203.
    Boeheim K, Speak JA, Frei E, et al. SQM1 antibody defines a surface membrane antigen in squamous carcinoma of the head and neck. Int J Cancer 1985; 36: 137–42PubMedCrossRefGoogle Scholar
  204. 204.
    Estaban F, Ruiz-Cabello F, Concha A, et al. Relationship of 4F2 antigen with local growth and metastatic potential of squamous cell carcinoma of the larynx. Cancer 1990; 66: 1493–8CrossRefGoogle Scholar
  205. 205.
    Teng YT, Nadimi H, Toto PD. Immunohistochemical localization of Leu-M1 carbohydrate antigen in human oral squamous cell carcinoma. J Oral Pathol Med 1989; 18: 502–5PubMedCrossRefGoogle Scholar
  206. 206.
    Ogawa Y, Inomata T, Nishioka A, et al. Changes in the Ki-67 labelling rates of head and neck squamous cell carcinomas during preoperative radiation therapy. Oncology 1992; 49: 450–3PubMedCrossRefGoogle Scholar
  207. 207.
    Fantozzi RD. Development of monoclonal antibodies with specificity to oral squamous cell carcinoma. Laryngoscope 1991; 101: 1076–80PubMedCrossRefGoogle Scholar
  208. 208.
    Shin DM, Voravud N, Ro JY, et al. Sequential increases in proliferating cell nuclear antigen expression in head and neck tumorigenesis: a potential biomarker. J Natl Cancer Inst 1993; 85: 971–8PubMedCrossRefGoogle Scholar
  209. 209.
    Schrijvers AHG, Gerretsen M, van Walsum M, et al. Potential for targeting head and neck squamous cell carcinoma with monoclonal antibody K984. Cancer Immunol Immunother 1992; 34: 252–8PubMedCrossRefGoogle Scholar
  210. 210.
    Schrijvers AH, Quak JJ, Uyterlinde AM, et al. MAb U36, a novel monoclonal antibody successful in immunotargeting of squamous cell carcinoma of the head and neck. Cancer Res 1993; 53(18): 4383–90PubMedGoogle Scholar
  211. 211.
    Quak J, Garretsen M, De Bree R, et al. Perspectives of monoclonal antibodies for detection and treatment of head and neck tumours. Anticancer Res 1993; 13(6B): 2533–9PubMedGoogle Scholar
  212. 212.
    Weidman E, Sacchi M, Plaisance S, et al. Receptors for interleukin 2 on human squamous cell carcinoma cell lines and tumor in situ. Cancer Res 1992; 52: 5963–70Google Scholar
  213. 213.
    Vlock DR, Toporowicz A, Arnold B, et al. Isolation and purification of a squamous cell carcinoma of the head and neck-associated antigen identified by autologous antibody. Biochim Biophys Acta 1993; 1181: 174–82PubMedCrossRefGoogle Scholar
  214. 214.
    Johnson JT, Rabin BS, Wagner RL. Prostaglandin E2 of the upper aerodigestive tract. Ann Otolarygol Rhinol Laryngol 1987; 96: 213–6Google Scholar
  215. 215.
    Bennett A, Carter RL, Stamford IF, et al. Prostaglandin-like material extracted from squamous carcinomas of the head and neck. Br J Cancer 1982; 41: 204–8CrossRefGoogle Scholar
  216. 216.
    Snyderman CH, Klapan I, Milanovich M, et al. Comparison of in vivo and in vitro prostaglandin E2 production by squamous cell carcinoma of the head and neck. Otolaryngol Head Neck Surg 1994; 111(3): 189–96PubMedCrossRefGoogle Scholar
  217. 217.
    Goodwin JS, Ceuppens J. Regulation of the immune response by prostaglandins. J Clin Immunol 1983; 3: 295–315PubMedCrossRefGoogle Scholar
  218. 218.
    Tan IB, Drexhage HA, Mullink R, et al. Immunohistochemical detection of retroviral-P15E-related material in carcinomas of the head and neck. Otolaryngol Head Neck Surg 1987; 96: 251–5PubMedGoogle Scholar
  219. 219.
    Nelson M, Nelson DS, Spradbrow PB, et al. Successful tumour immunotherapy: possible role of antibodies to anti-inflammatory factors produced by neoplasms. Clin Exp Immunol 1985; 61: 109–17PubMedGoogle Scholar
  220. 220.
    Mann EA, Spiro JD, Chen LL, et al. Cytokine expression by head and neck squamous cell carcinomas. Am J Surg 1992; 164: 567–73PubMedCrossRefGoogle Scholar
  221. 221.
    Hadden JW, Spreafico F. New approaches to immunotherapy. Springer Semin Immunopathol 1985; 8: 321–6PubMedCrossRefGoogle Scholar
  222. 222.
    Cortesina G, DeStefani A, Sacchi M, et al. Immunomodulation therapy for squamous cell carcinoma of the head and neck. Head Neck 1993; 15: 266–70PubMedCrossRefGoogle Scholar
  223. 223.
    Donaldson RC. Methotrexate plus Bacillus Calmette-Guerin (BCG) and isoniazid in the treatment of cancer of the head and neck. Am J Surg 1972; 124: 527–34PubMedCrossRefGoogle Scholar
  224. 224.
    Eastham RJ, Mason JM, Jennings BR, et al. T-cell rosette test in squamous cell carcinoma of the head and neck. Arch Otolaryngol 1976; 102: 171–5PubMedCrossRefGoogle Scholar
  225. 225.
    Suen JY, Richman SP, Livingston RB, et al. Results of BCG adjuvant immunotherapy in 100 patients with epidermoid carcinoma of the head and neck. Am J Surg 1977; 134: 474–8PubMedCrossRefGoogle Scholar
  226. 226.
    Bier J, Rapp HJ, Borsos T, et al. Randomized study on intratumoral BCG-cell wall preparation (CWP) therapy in patients with squamous cell carcinoma in the head and neck region. Cancer Immunol Immunother 1981; 12: 71–5CrossRefGoogle Scholar
  227. 227.
    Cheng VS, Suit MD, Wang CC, et al. Corynebacterium parvum - intra lymph node and intravenous - and radiation therapy in the treatment of the head and neck carcinoma. Cancer 1982; 49: 239–44PubMedCrossRefGoogle Scholar
  228. 228.
    Cunningham TJ, Antemann R, Paonessa D, et al. Adjuvant immuno- and/or chemotherapy with neuraminidase-treated autologous tumor vaccine and bacillus calmette-guerin for head and neck cancers. Ann NY Acad Sci 1986; 115: 339–44Google Scholar
  229. 229.
    Wanebo HJ, Hilal EY, Pinsky CM, et al. Randomized trial of levamisole in patients with squamous cancer of the head and neck: a preliminary report. Cancer Treat Rep 1978; 62: 1663–9PubMedGoogle Scholar
  230. 230.
    Olivari AJ, Glait HM, Guardo A, et al. Levamisole in squamous cell carcinoma of the head and neck. Cancer Treat Rep 1979; 63: 983–90PubMedGoogle Scholar
  231. 231.
    Balaram P, Padmanabhan TK, Vasudevan DM. Role of levamisole immunotherapy as an adjuvant to radiotherapy in oral cancer. II. Lymphocyte subpopulations. Neoplasma 1988; 35: 235–42PubMedGoogle Scholar
  232. 232.
    Blitzer A, Chun Huang C. The effect of indomethacin on the growth of epidermoid carcinoma of the palate in rats. Arch Otolaryngol 1983; 109: 719–23PubMedCrossRefGoogle Scholar
  233. 233.
    Hirsch B, Johnson JT, Rabin BS, et al. Immunostimulation of patients with head and neck cancer. Arch Otolaryngol 1983; 109: 298–301PubMedCrossRefGoogle Scholar
  234. 234.
    Panje WR. Regression of head and neck carcinoma with a prostaglandin-synthesis inhibitor. Arch Otolaryngol 1981; 107: 658–63PubMedCrossRefGoogle Scholar
  235. 235.
    Cross DS, Piatt JL, Juhn SK, et al. Administration of a prostaglandin synthetase inhibitor associated with an increased immune cell infiltrate in squamous cell carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg 1992; 118: 526–8PubMedCrossRefGoogle Scholar
  236. 236.
    Seder RH, Vaughan CW, Oh S-K, et al. Tumor regression and temporary restoration of immune response after plasmapheresis in a patient with recurrent oral cancer. Cancer 1987; 60: 318–25PubMedCrossRefGoogle Scholar
  237. 237.
    Seder RH, Vaughan CW, Katz AE, et al. Clinical and laboratory changes following plasmapheresis in 12 patients with squamous cancer of the head and neck. Prog Clin Biol Res 1990; 337: 347–9PubMedGoogle Scholar
  238. 238.
    Gray WC, Hasslinger BJ, Suter CM, et al. Suppression of cellular immunity by head and neck irradiation. Arch Otolaryngol Head Neck Surg 1986; 112: 1185–90PubMedCrossRefGoogle Scholar
  239. 239.
    Hadden EM, Malec P, Sosa M, et al. Mixed interleukins and thymosin fraction V synergistically induce T lymphocyte development in hydrocortisone-treated aged mice. Cell Immunol 1992; 144: 228–36PubMedCrossRefGoogle Scholar
  240. 240.
    Hadden JW, Malec P, Saha A, et al. Cytokine synergy in immunotherapy. In: Goldstein AL, Garaci E, editors. Combination therapies II. New York: Plenum Press, 1993: 1–10CrossRefGoogle Scholar
  241. 241.
    Wara WM, Neely MH, Ammann AJ, et al. Biologic modification of immunologic parameters in head and neck cancer patients with thymosin fraction V. In: Goldstein AL, Chirigos MA, editors. Lymphokines and thymic hormones: their potential utilization in cancer therapies. New York: Raven Press, 1981: 257–62Google Scholar
  242. 242.
    Schulof RS, Lloyd MJ, Cleary GA, et al. A randomized trial to evaluate the immunorestorative properties of synthetic thymosin-α1 in patients with lung cancer. J Biol Response Mod 1985; 4: 147–58PubMedGoogle Scholar
  243. 243.
    Goldstein AL. Thymosin α1: chemistry, mechanism of action and clinical applications. In: Goldstein AL, Garaci E, editors. Combination therapies II. New York: Plenum Press, 1993: 39–48CrossRefGoogle Scholar
  244. 244.
    Wolfe GT. Prospective randomized trial of thymosin alpha (Ta1) immune reconstitution in patients with advanced head and neck squamous carcinoma (HNSC): 5 year results. Proc Am Assoc Cancer Res 1989; 30: 261Google Scholar
  245. 245.
    Garaci E. Combination therapy with thymosin α1 and cytokines in the treatment of cancer and infectious diseases. In: Goldstein AL, Garaci E, editors. Combination therapies II. New York: Plenum Press; 1993: 49–60CrossRefGoogle Scholar
  246. 246.
    Ikic D, Padovan I, Brodarec I, et al. Application of human leucocyte interferon in patients with tumours of the head and neck. Lancet 1981; 9: 1025–7Google Scholar
  247. 247.
    Padovan I, Brodarec I, Ikic D, et al. Effect of interferon in therapy of skin and head and neck tumors. J Cancer Res Clin Oncol 1981; 100: 295–310PubMedCrossRefGoogle Scholar
  248. 248.
    Medenica R. Clinical results of leukocyte interferon-induced tumour regression in resistant human metastatic cancer. Cancer Drug Delivery 1985; 2: 53–76PubMedCrossRefGoogle Scholar
  249. 249.
    Connors JM, Andiman WA, Howarth CB, et al. Treatment of nasopharyngeal carcinoma with human leukocyte interferon. J Clin Oncol 1985; 3: 813–7PubMedGoogle Scholar
  250. 250.
    Fierro R, Johnson JT, Myers E, et al. Phase II trial of recombinant interferon-α in recurrent squamous cell carcinoma of the head and neck. Proc Am Soc Clin Oncol 1988; 29: 605Google Scholar
  251. 251.
    Agarwala S, Vlock D, Johnson JT, et al. Phase II trial of interferon-α in locally recurrent or metastatic head and neck cancer: results of ECOG trial P-Z386. Proc Am Soc Clin Oncol 1991; 32: 684Google Scholar
  252. 252.
    Vlock DR. Immunobiologic aspects of head and neck cancer. Head Neck Cancer 1991; 5: 797–820Google Scholar
  253. 253.
    Tamura T, Sasaki Y, Shinkai T, et al. Phase I study of combination therapy with interleukin 2 and beta-interferon in patients with advanced malignancy. Cancer Res 1989; 49: 730–5PubMedGoogle Scholar
  254. 254.
    Urba SG, Forastiere AA, Wolf GT, et al. Intensive recombinant interleukin-2 and alpha-interferon therapy in patients with advanced head and neck squamous carcinoma. Cancer 1993; 71: 2326–31PubMedCrossRefGoogle Scholar
  255. 255.
    Schantz SP, Clayman G, Racz T, et al. The in vivo biologic effect of interleukin 2 and interferon alpha on natural immunity in patients with head and neck cancer. Arch Otolaryngol Head Neck Surg 1990; 116: 1302–8PubMedCrossRefGoogle Scholar
  256. 256.
    Richtsmeier WJ, Koch WM, McGuire WP, et al. Phase I-II study of advanced head and neck squamous cell carcinoma patients treated with recombinant human interferon gamma. Arch Otolaryngol Head Neck Surg 1990; 116: 1271–7PubMedCrossRefGoogle Scholar
  257. 257.
    Dimery I, Jacobs C, Tseng A, et al. Recombinant interferon gamma in the treatment of recurrent nasopharyngeal carcinoma. Proc Am Soc Clin Oncol 1987; 28: 669Google Scholar
  258. 258.
    Pizza G, Viza D, De Vinci C, et al. Intra-lymphatic administration of interleukin-2 (IL-2) in cancer patients: a pilot study. Lymphokine Res 1988; 7: 45–8PubMedGoogle Scholar
  259. 259.
    Cortesina G, DeStefani A, Giovarelli M, et al. Treatment of recurrent squamous cell carcinoma of the head and neck with low doses of interleukin-2 injected perilymphatically. Cancer 1988; 62: 2482–5PubMedCrossRefGoogle Scholar
  260. 260.
    Musiani P, DeCampora E, Valitutti S, et al. Effect of low doses of interleukin-2 injected perilymphatically and peritumorally in patients with advanced primary head and neck squamous cell carcinoma. J Biol Response Mod 1989; 8: 571–8PubMedGoogle Scholar
  261. 261.
    Valente G, DeStefani A, Jemma C, et al. Infiltrating leukocyte populations and T lymphocyte subsets in head and neck squamous cell carcinomas from patients receiving perilymphatic injections of recombinant interleukin-2. Mod Pathol 1990; 6: 702–8Google Scholar
  262. 262.
    Cortesina G, DeStefani A, Galeazzi E, et al. The effects of preoperative local interleukin-2 injections in patients with head and neck carcinoma: an immunologic study. Acta Otolaryngol 1991; 111: 428–33PubMedCrossRefGoogle Scholar
  263. 263.
    Cortesina G, DeStefani A, Galeazzi E, et al. Interleukin-2 injected around tumor draining lymph nodes in head and neck cancer. Head Neck 1991; 13: 125–31PubMedCrossRefGoogle Scholar
  264. 264.
    Mattijssen V, DeMulder PH, Shornagel HJ, et al. Clinical and immunopathological results of phase II study of perilymphatically injected recombinant interleukin-2 in locally advanced, non-pretreated head and neck squamous cell carcinomas. J Immunother 1991; 10: 63–8PubMedCrossRefGoogle Scholar
  265. 265.
    Whiteside TL, Letessier E, Hirabayashi H, et al. Evidence for local and systemic activation of immune cells by peritumoral injections of interleukin 2 in patients with advanced squamous cell carcinoma of the head and neck. Cancer Res 1993; 53(23): 5654–62PubMedGoogle Scholar
  266. 266.
    Cortesina G, De Stefani A, Galeazzi E, et al. Temporary regression of recurrent squamous cell carcinoma of the head and neck is achieved with a low but not high dose of recombinant interleukin 2 injected perilymphatically. Br J Cancer 1994; 69: 572–6PubMedCrossRefGoogle Scholar
  267. 267.
    Squadrelli-Saraceno M, Rivoltini L, Cantu G, et al. Local adoptive immunotherapy of advanced head and neck tumors with LAK cells and interleukin-2. Tumori 1990; 76: 566–71PubMedGoogle Scholar
  268. 268.
    Saito T, Yoda J, Tabata T. Local administration trials of interleukin-2 for head and neck cancer. Auris Nasus Larynx 1991; 18: 169–78PubMedCrossRefGoogle Scholar
  269. 269.
    Sawaki S. A phase 2 study of recombinant interleukin 2 (S-6820) for head and neck cancer. Jpn J Cancer Clin 1990; 36: 111–20Google Scholar
  270. 270.
    Dadian G, Riches PG, Henderson DC, et al. Immune changes in peripheral blood resulting from locally directed interleukin-2 therapy in squamous cell carcinoma of the head and neck. Eur J Cancer 1993; 29(1): 29–43CrossRefGoogle Scholar
  271. 271.
    Vlock DR, Snyderman CH, Johnson JT, et al. Phase Ib trial of the effect of peritumoral and intranodal injections of interleukin-2 in patients with advanced squamous cell carcinoma of the head and neck: an Eastern Cooperative Oncology Group trial. J Immunother 1994; 15(2): 134–9CrossRefGoogle Scholar
  272. 272.
    Selvaggi KJ, Vlock DR, Johnson JT, et al. Phase Ib trial of peritumoral and intranodal injections of IL-2 in patients with advanced squamous cell carcinoma of the head and neck: preliminary results. Proc Am Soc Clin Oncol 1990; 32: 691Google Scholar
  273. 273.
    Dimery I, Martin T, Bradley E, et al. Phase I trial of interleukin-2 plus cisplatin and 5-FU in recurrent or advanced squamous cell carcinoma of the head and neck. Proc Am Soc Clin Oncol 1989; 30: 660Google Scholar
  274. 274.
    Valone FH, Gandara DR, Deisseroth AB, et al. Interleukin-2, cisplatin, and 5-fluorouracil for patients with non-small cell lung and head/neck carcinomas. J Immunother 1991; 10: 207–13PubMedCrossRefGoogle Scholar
  275. 275.
    Ikawa T, Eura M, Fukiage T, et al. Adoptive immunotherapy by intra-arterial infusion of ATLAK or alloTLAK cells in patients with head and neck cancer. Gan To Kagaku Ryoho 1989; 16: 1438–47PubMedGoogle Scholar
  276. 276.
    Playfair JHL, Heath AQ. Cytokines - the new generation of adjuvants for vaccines. In: Masihi KN, Lange W, editors. Immunotherapeutic prospects for infectious diseases. Berlin: Springer Verlag, 1990: 337–45CrossRefGoogle Scholar
  277. 277.
    Kelly RH, Wolstencroft RA, Dumonde DC, et al. Role of lymphocyte activation products (LAP) in cell-mediated immunity. Clin Exp Immunol 1972; 10: 49–65PubMedGoogle Scholar
  278. 278.
    Pulley MS, Nagendran V, Edwards JM, et al. Intravenous, intralesional and endolymphatic administration of lymphokines in human cancer. Lymphokine Res 1986; 5: 157–70Google Scholar
  279. 279.
    North RJ. The murine antitumor immune response and its therapeutic manipulation. Adv Immunol 1984; 35: 89–155PubMedCrossRefGoogle Scholar
  280. 280.
    Berd D, Maguire HC, Mastrangelo MJ. Potentiation of human cell-mediated and humoral immunity by low dose cyclophosphamide. Cancer Res 1984; 44: 5439–43PubMedGoogle Scholar
  281. 281.
    Hadden JW. T-cell adjuvancy. Int J Immunopharmacol 1994; 16: 703–10PubMedCrossRefGoogle Scholar
  282. 282.
    Tepper RI. Cytokines and strategies for anticancer vaccines. Contemp Oncol 1993; 6: 38–53Google Scholar
  283. 283.
    Scott P. IL-12: initiation cytokine for cell-mediated immunity. Science 1993; 260: 496–7PubMedCrossRefGoogle Scholar
  284. 284.
    Freeman SM, Zwiebel JA. Gene therapy of cancer. Cancer Invest 1993; 11: 676–88PubMedCrossRefGoogle Scholar
  285. 285.
    Smith T. Histamine type 2-receptor antagonists and cancer immunotherapy. Compr Ther 1990; 16: 8–13PubMedGoogle Scholar
  286. 286.
    Hadden JW. Thymic endocrinology. Int J Immunopharmacol 1992; 14: 345–52PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1995

Authors and Affiliations

  • John W. Hadden
    • 1
  1. 1.Department of Internal Medicine, Division of ImmunopharmacologyUniversity of South FloridaTampaUSA

Personalised recommendations