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Trials and tribulations of immunotherapy as a treatment option for patients with squamous cell carcinoma of the head and neck

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Abstract

Head and neck squamous cell carcinoma (HNSCC) is an aggressive epithelial malignancy that is the sixth most common neoplasm in the world. Despite numerous advances in treatments involving surgery, radiation, and chemotherapy, the 5-year survival has remained at less than 50% for the last 30 years primarily due to local recurrences [66]. Consequently, the possibility of developing immunotherapeutic approaches as a treatment for HNSCC has gained interest. The present review has 3 objectives pertaining to immunotherapeutic means to treat HNSCC patients: (1) to summarize the feasibility of such approaches, (2) to provide an overview of the obstacles to attaining protective immune reactivity, and (3) to consider how these obstacles can be overcome to stimulate immune reactivity to HNSCC. These objectives will also be considered in the context of what lessons have been learned from immunotherapeutic trials for other solid malignancies and the applicability of this information to HNSCC.

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References

  1. Ajani JA, Kelsen DP, Haller D, Hargraves K, Healey D (2000) A multi-institutional phase II study of BMS-182248-01 (BR96-doxorubicin conjugate) administered every 21 days in patients with advanced gastric adenocarcinoma. Cancer J 6:78–81

    CAS  PubMed  Google Scholar 

  2. Alexander JP, Kudoh S, Melsop KA, Hamilton TA, Edinger MG, Tubbs RR, Sica D, Tuason L, Klein E, Budowski RM, Finke JH (1993) T-cells infiltrating renal cell carcinoma display a poor proliferative response even though they can produce interleukin 2 and express interleukin 2 receptors. Cancer Res 53:1380–1387

    Google Scholar 

  3. Almand B, Resser JR, Lindman B, Nadaf S, Clark JI, Kwon ED, Carbone DP, Gabrilovich DI (2000) Clinical significance of defective dendritic cell differentiation in cancer. Clin Cancer Res 6:1755–1766

    CAS  PubMed  Google Scholar 

  4. Almand B, Clark JI, Nikitina E, van Beynen J, English NR, Knight SC, Carbone DP, Gabrilovich DI (2001) Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J Immunol 166:678–689

    CAS  PubMed  Google Scholar 

  5. Baars A, Claessen AM, Wagstaff J, Giaccone G, Scheper RJ, Meijer S, Schakel MJ, Gall HE, Meijer CJ, Vermorken JB, Pinedo HM, van Den Eertwegh AJ (2002) A phase II study of active specific immunotherapy and 5-FU/Leucovorin as adjuvant therapy for stage III colon carcinoma. Br J Cancer 86:1230–1234

    Article  CAS  PubMed  Google Scholar 

  6. Balch CM, Dougherty PA, Tilden AB (1982) Excessive prostaglandin E2 production by suppressor monocytes in head and neck cancer patients. Ann Surg 196:645–650

    CAS  PubMed  Google Scholar 

  7. Banchereau J, Palucka AK, Dhodapkar M, Burkeholder S, Taquet N, Rolland A, Taquet S, Coquery S, Wittkowski KM, Bhardwaj N, Pineiro L, Steinman R, Fay J (2001) Immune and clinical responses in patients with metastatic melanoma to CD34+ progenitor-derived dendritic cell vaccine. Cancer Res 61:6451–6458

    CAS  PubMed  Google Scholar 

  8. Banich JC, Kolesiak K, Young MR (2003) Chemoattraction of CD34+ progenitor cells and dendritic cells to the site of tumor excision as the first step of an immunotherapeutic approach to target residual tumor cells. J Immunother 26:31–40

    Article  CAS  PubMed  Google Scholar 

  9. Barrera JL, Verastegui E, Meneses A, Zinser J, de LG, Hadden JW (2000) Combination immunotherapy of squamous cell carcinoma of the head and neck: a phase II trial. Arch Otolaryngol Head Neck Surg 126:345–351

    Google Scholar 

  10. Bier H, Hoffmann T, Haas I, van Lierop A (1998) Anti-(epidermal growth factor) receptor monoclonal antibodies for the induction of antibody-dependent cell-mediated cytotoxicity against squamous cell carcinoma lines of the head and neck. Cancer Immunol Immunother 46:167–173

    Article  CAS  PubMed  Google Scholar 

  11. Bier H, Hoffmann T, Hauser U, Wink M, Ochler M, Kovar A, Muser M, Knecht R (2001) Clinical trial with escalating doses of the antiepidermal growth factor receptor humanized monoclonal antibody EMD 72 000 in patients with advanced squamous cell carcinoma of the larynx and hypopharynx. Cancer Chemother Pharmacol 47:519–524

    Article  CAS  PubMed  Google Scholar 

  12. Burch PA, Breen JK, Buckner JC, Gastineau DA, Kaur JA, Laus RL, Padley DJ, Peshwa MV, Pitot HC, Richardson RL, Smits BJ, Sopapan P, Strang G, Valone FH, Vuk-Pavlovic S (2000) Priming tissue-specific cellular immunity in a phase I trial of autologous dendritic cells for prostate cancer. Clin Cancer Res 6:2175–2182

    CAS  PubMed  Google Scholar 

  13. Chang AE, Li Q, Jiang G, Teknos TN, Chepeha DB, Bradford CR (2003) Generation of vaccine-primed lymphocytes for the treatment of head and neck cancer. Head Neck 25:198–209

    Article  PubMed  Google Scholar 

  14. Cho Y, Miyamoto M, Kato K, Fukunaga A, Shichinohe T, Kawarada Y, Hida Y, Oshikiri T, Kurokawa T, Suzuoki M, Nakakubo Y, Hiraoka K, Murakami S, Shinohara T, Itoh T, Okushiba S, Kondo S, Katoh H (2003) CD4+ and CD8+ T cells cooperate to improve prognosis of patients with esophageal squamous cell carcinoma. Cancer Res 63:1555–1559

    CAS  PubMed  Google Scholar 

  15. Corinti S, Albanesi C, la Sala A, Pastore S, Girolomoni G (2001) Regulatory activity of autocrine IL-10 on dendritic cell functions. J Immunol 166:4312–4318

    CAS  PubMed  Google Scholar 

  16. Cox GW, Melillo G, Chattopadhyay U, Mullet D, Fertel RH, Varesio L (1992) Tumor necrosis factor-α-dependent production of reactive nitrogen intermediates mediates IFN-γ plus IL-2-induced murine macrophage tumoricidal activity. J Immunol 149:3290–3296

    CAS  PubMed  Google Scholar 

  17. Cross DS, Platt JL, Juhn SK, Bach FH, Adams GL (1992) 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 118:526–528

    Google Scholar 

  18. Day KV, Li D, Liu S, Guo M, O’Malley BW Jr (2001) Granulocyte-macrophage colony-stimulating factor in a combination gene therapy strategy for head and neck cancer. Laryngoscope 111:801–806

    Google Scholar 

  19. De Paola F, Ridolfi R, Riccobon A, Flamini E, Barzanti F, Granato AM, Mordenti GL, Medri L, Vitali P, Amadori D (2003) Restored T-cell activation mechanisms in human tumour-infiltrating lymphocytes from melanomas and colorectal carcinomas after exposure to interleukin-2. Br J Cancer 88:320–326

    Article  PubMed  Google Scholar 

  20. Finke J, Ferrone S, Frey A, Mufson A, Ochoa A (1999) Where have all the T cells gone? mechanisms of immune evasion by tumors. Immunol Today 20:158–160

    CAS  PubMed  Google Scholar 

  21. Fiorentino D, Zlotnik A, Vieira P, Mosmann TR, Howard M, Moore KW, O’Garra A (1991) IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells. J Immunol 146:3444–3451

    CAS  PubMed  Google Scholar 

  22. Fong L, Brockstedt D, Benike C, Breen JK, Strang G, Ruegg CL, Engleman EG (2001) Dendritic cell-based xenoantigen vaccination for prostate cancer immunotherapy. J Immunol 167:7150–7156

    CAS  PubMed  Google Scholar 

  23. Gabrilovich DI, Nadaf S, Corak J, Berzofsky JA, Carbone DP (1996) Dendritic cells in antitumor immune responses. II. Dendritic cells grown from bone marrow precursors, but not mature DC from tumor-bearing mice, are effective antigen carriers in the therapy of established tumors. Cell Immunol 170:111–119

    Article  CAS  PubMed  Google Scholar 

  24. Gabrilovich D, Ishida T, Oyama T, Ran S, Kravtsov V, Nadaf S, Carbone DP (1998) Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo. Blood 92:4150–4166

    CAS  PubMed  Google Scholar 

  25. Gabrilovich DI, Velders MP, Sotomayor EM, Kast WM (2001) Mechanism of immune dysfunction in cancer mediated by immature Gr-1+ myeloid cells. J Immunol 166:5398–5406

    CAS  PubMed  Google Scholar 

  26. Garrity T, Pandit R, Wright MA, Benefield J, Young MRI (1997) Increased presence of CD34+ cells in the peripheral blood of head and neck cancer patients and their differentiation into CD1a+ cells. Int J Cancer 73:663–669

    CAS  PubMed  Google Scholar 

  27. Geiger JD, Hutchinson RJ, Hohenkirk LF, McKenna EA, Yanik GA, Levine JE, Chang AE, Braun TM, Mule JJ (2001) Vaccination of pediatric solid tumor patients with tumor lysate-pulsed dendritic cells can expand specific T cells and mediate tumor regression. Cancer Res 61:8513–8519

    PubMed  Google Scholar 

  28. Gleich LL, Li YQ, Li S, Gluckman JL, Stambrook PJ (2003) Alloantigen gene therapy for head and neck cancer: Evaluation of animal models. Head Neck 25:274–279

    Article  PubMed  Google Scholar 

  29. Gotte K, Usener D, Riedel F, Hormann K, Schadendorf D, Eichmuller S (2002) Tumor-associated antigens as possible targets for immune therapy in head and neck cancer: comparative mRNA expression analysis of RAGE and GAGE genes. Acta Otolaryngol 122:546–552

    Google Scholar 

  30. Grandis JR, Falkner DM, Melhem MF, Gooding WE, Drenning SD, Morel PA (2000) Human leukocyte antigen class I allelic and haplotype loss in squamous cell carcinoma of the head and neck: clinical and immunogenetic consequences. Clin Cancer Res 6:2794–2802

    CAS  PubMed  Google Scholar 

  31. Hadden J, Verastegui E, Barrera JL, Kurman M, Meneses A, Zinser JW, de la GJ, Hadden E (2003) A trial of IRX-2 in patients with squamous cell carcinomas of the head and neck. Int Immunopharmacol 3:1073–1081

    Article  CAS  PubMed  Google Scholar 

  32. Heimdal JH, Aarstad HJ, Klementsen B, Olofsson J (1999) Peripheral blood mononuclear cell (PBMC) responsiveness in patients with head and neck cancer in relation to tumour stage and prognosis. Acta Otolaryngol 119:281–284

    Google Scholar 

  33. Javia LR, Rosenberg SA (2003) CD4+CD25+ suppressor lymphocytes in the circulation of patients immunized against melanoma antigens. J Immunother 26:85–93

    Article  CAS  PubMed  Google Scholar 

  34. Kalinski P, Hilkens CMU, Wierenga EA, Kapsenberg ML (2000) T-cell priming by type-1 and type-2 polarized dendritic cells: the concept of a third signal. Immunology Today 20:561–567

    Article  Google Scholar 

  35. Karagiannis SN, Wang Q, East N, Burke F, Riffard S, Bracher MG, Thompson RG, Durham SR, Schwartz LB, Balkwill FR, Gould HJ (2003) Activity of human monocytes in IgE antibody-dependent surveillance and killing of ovarian tumor cells. Eur J Immunol 33:1030–1040

    Article  CAS  PubMed  Google Scholar 

  36. Kass ES, Greiner JW, Kantor JA, Tsang KY, Guadagni F, Chen Z, Clark B, De Pascalis R, Schlom J, Van Waes C (2002) Carcinoembryonic antigen as a target for specific antitumor immunotherapy of head and neck cancer. Cancer Res 62:5049–5057

    CAS  PubMed  Google Scholar 

  37. Kienstra MA, Neel HB, Strome SE, Roche P (2003) Identification of NY-ESO-1, MAGE-1, and MAGE-3 in head and neck squamous cell carcinoma. Head Neck 25:457–463

    Article  PubMed  Google Scholar 

  38. Kobie JJ, Wu RS, Kurt RA, Lou S, Adelman MK, Whitesell LJ, Ramanathapuram LV, Arteaga CL, Akporiaye ET (2003) Transforming growth factor β inhibits the antigen-presenting functions and antitumor activity of dendritic cell vaccines. Cancer Res 63:1860–1864

    CAS  PubMed  Google Scholar 

  39. Kondo Y, Uchino J, Sawaguchi Y, Shirato H, Gondo H, Hase T, Saito I, Higashi T, Hosokawa M, Kobayashi H (1996) Evaluation of multi skin test in colorectal cancer patients and effects of serum immunosuppressive factor and cytokine production of peripheral mononuclear cells. Am J Clin Oncol 19:159–163

    Article  CAS  PubMed  Google Scholar 

  40. Kuge S, Miura Y, Nakamura Y, Mitomi T, Habu S, Nishimura T (1995) Superantigen-induced human CD4+ helper/killer T cell phenomenon. Selective induction of Th1 helper/killer T cells and application to tumor immunotherapy. J Immunol 154:1777–1785

    CAS  PubMed  Google Scholar 

  41. Lang S, Lauffer L, Clausen C, Lohr I, Schmitt B, Holzel D, Wollenberg B, Gires O, Kastenbauer E, Zeidler R (2003) Impaired monocyte function in cancer patients: restoration with a cyclooxygenase-2 inhibitor. FASEB J 17:286–288

    CAS  PubMed  Google Scholar 

  42. Lathers DMR, Lubbers E, Wright MA, Young MRI (1999) Dendritic cell differentiation pathways of CD34+ cells from the peripheral blood of head and neck cancer patients. J Leuko Biol 65:623–628

    CAS  PubMed  Google Scholar 

  43. Lathers DMR, Achille NJ, Young MRI (2001) Phase 1B study of 25-hydroxyvitamin D3 treatment to diminish suppressor cells in head and neck cancer patients. Human Immunol 62:1282–1293

    Article  CAS  Google Scholar 

  44. Li D, Shugert E, Guo M, Bishop JS, O’Malley BW Jr (2001) Combination nonviral interleukin 2 and interleukin 12 gene therapy for head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 127:1319–1324

    Google Scholar 

  45. Lodge PA, Jones LA, Bader RA, Murphy GP, Salgaller ML (2000) Dendritic cell-based immunotherapy of prostate cancer: Immune monitoring of a phase II clinical trial. Cancer Res 60:829–833

    CAS  PubMed  Google Scholar 

  46. Makower D, Sparano JA, Wadler S, Fehn K, Landau L, Wissel P, Versola M, Mani S (2003) A pilot study of edrecolomab (Panorex, 17-1A antibody) and capecitabine in patients with advanced or metastatic adenocarcinoma. Cancer Invest 21:177–184

    Article  CAS  PubMed  Google Scholar 

  47. Mandpe AH, Tsung K, Norton JA (2003) Cure of an established nonimmunogenic tumor, SCC VII, with a novel interleukin 12-based immunotherapy regimen in C3H mice. Arch Otolaryngol Head Neck Surg 129:786–792

    Article  PubMed  Google Scholar 

  48. Mann EA, Spiro JD, Chen LL, Kreutzer DL (1992) Cytokine expression by head and neck squamous cell carcinomas. Am J Surg 164:567–573

    CAS  PubMed  Google Scholar 

  49. Meneses A, Verastegui E, Barrera JL, de la GJ, Hadden JW (2003) Lymph node histology in head and neck cancer: impact of immunotherapy with IRX-2. Int Immunopharmacol 3:1083–1091

    Article  CAS  PubMed  Google Scholar 

  50. Miller G, Lahrs S, Pillarisetty VG, Shah AB, DeMatteo RP (2002) Adenovirus infection enhances dendritic cell immunostimulatory properties and induces natural killer and T-cell-mediated tumor protection. Cancer Res 62:5260–5266

    CAS  PubMed  Google Scholar 

  51. Miller G, Pillarisetty VG, Shah AB, Lahrs S, Xing Z, DeMatteo RP (2002) Endogenous granulocyte-macrophage colony-stimulating factor overexpression in vivo results in the long-term recruitment of a distinct dendritic cell population with enhanced immunostimulatory function. J Immunol 169:2875–2885

    CAS  PubMed  Google Scholar 

  52. Mizoguchi H, O’Shea JJ, Longo DL, Loeffler CM, McVicar DW, Ochoa AC (1992) Alterations in signal transduction molecules in T lymphocytes from tumor-bearing mice. Science 258:1795–1798

    CAS  PubMed  Google Scholar 

  53. Monji M, Senju S, Nakatsura T, Yamada K, Sawatsubashi M, Inokuchi A, Nishimura Y (2002) Head and neck cancer antigens recognized by the humoral immune system. Biochem Biophys Res Commun 294:734–741

    Article  CAS  PubMed  Google Scholar 

  54. Naundorf S, Preithner S, Mayer P, Lippold S, Wolf A, Hanakam F, Fichtner I, Kufer P, Raum T, Riethmuller G, Baeuerle PA, Dreier T (2002) In vitro and in vivo activity of MT201, a fully human monoclonal antibody for pancarcinoma treatment. Int J Cancer 100:101–110

    Article  CAS  PubMed  Google Scholar 

  55. Neuner A, Schindel M, Wildenberg U, Muley T, Lahm H, Fischer JR (2002) Prognostic significance of cytokine modulation in non-small cell lung cancer. Int J Cancer 101:287–292

    Article  CAS  PubMed  Google Scholar 

  56. Ohm JE, Shurin MR, Esche C, Lotze MT, Carbone DP, Gabrilovich DI (1999) Effect of vascular endothelial growth factor and FLT3 ligand on dendritic cell generation in vivo. J Immunol 163:3260–3268

    CAS  PubMed  Google Scholar 

  57. Pandit R, Lathers DM, Beal NM, Garrity T, Young MRI (2000) CD34+ immune suppressive cells in the peripheral blood of patients with head and neck cancer. Ann Otol Rhinol Laryngol 109:749–754

    Google Scholar 

  58. Prechel MM, Lozano Y, Wright MA, Ihm J, Young MRI (1995) Ineffective immune enhancement by IL-12 in tumor-bearing mice whose immune depression is mediated by suppressive granulocyte-macrophage progenitor cells. Cancer Lett 92:235–242

    Article  CAS  PubMed  Google Scholar 

  59. Qin H, Valentino J, Manna S, Tripathi PK, Bhattacharya-Chatterjee M, Foon KA, O’Malley BW Jr, Chatterjee SK (2001) Gene therapy for head and neck cancer using vaccinia virus expressing IL-2 in a murine model, with evidence of immune suppression. Mol Ther 4:551–558

    Article  CAS  PubMed  Google Scholar 

  60. Reichert TE, Day R, Wagner EM, Whiteside TL (1998) Absent or low expression of the zeta chain in T cells at the tumor site correlates with poor survival in patients with oral carcinoma. Cancer Res 58:5344–5347

    CAS  PubMed  Google Scholar 

  61. Rhee CS, Sen M, Lu D, Wu C, Leoni L, Rubin J, Corr M, Carson DA (2002) Wnt and frizzled receptors as potential targets for immunotherapy in head and neck squamous cell carcinomas. Oncogene 21:6598–6605

    Article  CAS  PubMed  Google Scholar 

  62. Schechter NR, Yang DJ, Azhdarinia A, Kohanim S, Wendt R III, Oh CS, Hu M, Yu DF, Bryant J, Ang KK, Forster KM, Kim EE, Podoloff DA (2003) Assessment of epidermal growth factor receptor with 99mTc-ethylenedicysteine-C225 monoclonal antibody. Anticancer Drugs 14:49–56

    Article  CAS  PubMed  Google Scholar 

  63. Scioscia KA, Snyderman CH, Rueger R, Reddy J, D’Amico F, Comsa S, Collins B (1997) Role of arachidonic acid metabolites in tumor growth inhibition by nonsteroidal antiinflammatory drugs. Am J Otolaryngol 18:1–8

    Google Scholar 

  64. Sheu BC, Lin RH, Lien HC, Ho HN, Hsu SM, Huang SC (2001) Predominant Th2/Tc2 polarity of tumor-infiltrating lymphocytes in human cervical cancer. J Immunol 167:2972–2978

    CAS  PubMed  Google Scholar 

  65. Shibuya TY, Wei WZ, Zormeier M, Ensley J, Sakr W, Mathog RH, Meleca RJ, Yoo GH, June CH, Levine BL, Lum LG (2000) Anti-CD3/anti-CD28 bead stimulation overcomes CD3 unresponsiveness in patients with head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 126:473–479

    Google Scholar 

  66. Shin DM, Lippman SM (1999) Paclitaxel-based chemotherapy for recurrent and/or metastatic head and neck squamous cell carcinoma: current and future directions. Semin Oncol 26:100–105

    CAS  PubMed  Google Scholar 

  67. Shin DM, Donato NJ, Perez-Soler R, Shin HJ, Wu JY, Zhang P, Lawhorn K, Khuri FR, Glisson BS, Myers J, Clayman G, Pfister D, Falcey J, Waksal H, Mendelsohn J, Hong WK (2001) Epidermal growth factor receptor-targeted therapy with C225 and cisplatin in patients with head and neck cancer. Clin Cancer Res 7:1204–1213

    CAS  PubMed  Google Scholar 

  68. Suzuki S, Mita S, Kamohara H, Sakamoto K, Ishiko T, Ogawa M (2001) IL-6 and IFN-γ regulation of IL-10 production by human colon carcinoma cells. Int J Oncol 18:581–586

    CAS  PubMed  Google Scholar 

  69. Thomas GR, Chen Z, Enamorado I, Bancroft C, Van Waes C (2000) IL-12- and IL-2-induced tumor regression in a new murine model of oral squamous-cell carcinoma is promoted by expression of the CD80 co-stimulatory molecule and interferon-γ. Int J Cancer 86:368–374

    CAS  PubMed  Google Scholar 

  70. Toomey D, Harmey J, Condron C, Kay E, Bouchier-Hayes D (1999) Phenotyping of immune cell infiltrates in breast and colorectal tumours. Immunol Invest 28:29–41

    CAS  PubMed  Google Scholar 

  71. Uno M, Otsuki T, Kurebayashi J, Sakaguchi H, Isozaki Y, Ueki A, Yata K, Fujii T, Hiratsuka J, Akisada T, Harada T, Imajo Y (2001) Anti-HER2-antibody enhances irradiation-induced growth inhibition in head and neck carcinoma. Int J Cancer 94:474–479

    Article  CAS  PubMed  Google Scholar 

  72. Vujanovic NL, Yasumura S, Hirabayashi H, Lin W, Watkins S, Herberman RB, Whiteside TL (1995) Antitumor activities of subsets of human IL-2-activated natural killer cells in solid tissues. J Immunol 154:281–289

    CAS  PubMed  Google Scholar 

  73. Wanebo HJ, Riley T, Karz D, Pace RC, Johns ME, Cantrell RW (1988) Indomethacin sensitive suppressor-cell activity in head and neck cancer patients. The role of the adherent mononuclear cell. Cancer 61:462–474

    CAS  PubMed  Google Scholar 

  74. Wiers K, Wright MA, Vellody K, Young MRI (1998) Failure of tumor-reactive lymph node cells to kill tumor in the presence of immune suppressive CD34+ cells can be overcome with vitamin D3 treatment to diminish CD34+ cell levels. Clin Exp Med 16:275–282

    Article  CAS  Google Scholar 

  75. Wiers KM, Lathers DM, Wright MA, Young MRI (2000) Vitamin D3 treatment to diminish the levels of immune suppressive CD34+ cells increases the effectiveness of adoptive immunotherapy. J Immunother 23:115–124

    Article  CAS  PubMed  Google Scholar 

  76. Winter H, Hu HM, Poehlein CH, Huntzicker E, Osterholzer JJ, Bashy J, Lashley D, Lowe B, Yamada J, Alvord G, Urba WJ, Fox BA (2003) Tumour-induced polarization of tumour vaccine-draining lymph node T cells to a type 1 cytokine profile predicts inherent strong immunogenicity of the tumour and correlates with therapeutic efficacy in adoptive transfer studies. Immunology 108:409–419

    Article  CAS  PubMed  Google Scholar 

  77. Wojtowiczpraga S (1997) Reversal of tumor-induced immunosuppression: a new approach to cancer therapy. J Immunother 20:165–177

    CAS  PubMed  Google Scholar 

  78. Wright MA, Wiers K, Vellody K, Djordjevic D, Young MRI (1998) Stimulation of immune suppressive CD34+ cells from normal bone marrow by Lewis lung carcinoma tumors. Cancer Immunol Immunother 46:253–260

    CAS  PubMed  Google Scholar 

  79. Yoshino I, Yano T, Murata M, Ishida T, Sugimachi K, Kimura G (1992) Tumor-reactive T-cells accumulate in lung cancer tissues but fail to respond due to tumor cell-derived factor. Cancer Res 52:775–781

    CAS  PubMed  Google Scholar 

  80. Young MR, Dizer M (1983) Enhancement of immune function and tumor growth inhibition by antibodies against prostaglandin E2. Immunol Comm 12:11–23

    CAS  Google Scholar 

  81. Young MR, Lathers DM (1999) Myeloid progenitor cells mediate immune suppression in patients with head and neck cancers. Int J Immunopharmacol 21:241–252

    Article  CAS  PubMed  Google Scholar 

  82. Young MR, Young ME (1989) Effects of fish oil diets on prostaglandin-dependent and myelopoiesis-associated immune suppressor mechanisms of mice bearing metastatic Lewis lung carcinoma tumors. Cancer Res 49:1931–1936

    CAS  PubMed  Google Scholar 

  83. Young MRI, Schmidt-Pak A, Wright MA, Matthews JP, Collins SL, Petruzzelli G (1995) Mechanisms of immune suppression in patients with head and neck cancer: presence of immune suppressive CD34+ cells in cancers that secrete granulocyte-macrophage colony-stimulating factor. Clin Cancer Res 1:95–103

    CAS  PubMed  Google Scholar 

  84. Young MRI, Wright MA, Lozano Y, Matthews JP, Benefield J, Prechel MM (1996) Mechanisms of immune suppression in patients with head and neck cancer: influence on the immune infiltrate of the cancer. Int J Cancer 67:333–338

    CAS  PubMed  Google Scholar 

  85. Young MRI, Wright MA, Matthews JP, Malik I, Prechel M (1996) Suppression of T cell proliferation by tumor-induced granulocyte-macrophage progenitor cells producing transforming growth factor-β and nitric oxide. J Immunol 156:1916–1922

    CAS  PubMed  Google Scholar 

  86. Young MRI, Wright MA, Lozano Y, Prechel MM, Benefield J, Leonetti JP, Collins SL, Petruzzelli GJ (1997) Increased recurrence and metastasis in patients whose primary head and neck squamous cell carcinomas secreted granulocyte-macrophage colony-stimulating factor and contained CD34+ natural suppressor cells. Int J Cancer 74:69–74

    CAS  PubMed  Google Scholar 

  87. Young MRI, Wright MA, Pandit R (1997) Myeloid differentiation treatment to diminish the presence of immune suppressive CD34+ cells within human head and neck squamous cell carcinomas. J Immunol 159:990–996

    CAS  PubMed  Google Scholar 

  88. Young MR, Wright MA, Lathers DM, Messingham KA (1999) Increased resistance to apoptosis by bone marrow CD34+ progenitor cells from tumor-bearing mice. Int J Cancer 82:609–615

    Article  CAS  PubMed  Google Scholar 

  89. Young MRI, Wright MA, Vellody K, Lathers DMR (1999) Skewed differentiation of bone marrow CD34+ cells of tumor bearers from dendritic toward monocytic cells, and the induction of differentiation toward dendritic cells by 1α,25-dihydroxyvitamin D3. Int J Immunopharmacol 675–688

  90. Young MRI, Petruzzelli G, Kolesiak K, Lathers DMR, Lingen MW, Gabrilovich D (2001) Human squamous cell carcinomas of the head and neck chemoattract immune suppressive CD34+ progenitor cells. Human Immunol 62:332–341

    Article  CAS  Google Scholar 

  91. Zou JP, Morford LA, Chougnet C, Dix AR, Brooks AG, Torres N, Shuman JD, Coligan JE, Brooks WH, Roszman TL, Shearer GM (1999) Human glioma-induced immunosuppression involves soluble factor(s) that alters monocyte cytokine profile and surface markers. J Immunol 162:4882–4892

    CAS  PubMed  Google Scholar 

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Young, M.R.I. Trials and tribulations of immunotherapy as a treatment option for patients with squamous cell carcinoma of the head and neck. Cancer Immunol Immunother 53, 375–382 (2004). https://doi.org/10.1007/s00262-003-0456-x

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