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Tumour-infiltrating lymphocytes mediate lysis of autologous squamous cell carcinomas of the head and neck

  • Original Article
  • Squamous Cell Carcinoma, Head and Neck, TIL, T Cells, MHC Class I, p53, HPV, IFNγ
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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Tumour-infiltrating lymphocytes (TIL) and tumours from six patients with squamous cell carcinomas of the head and neck (SCCHN) were investigated. The six tumours all expressed major histocompatibility complex (MHC) class I antigens both in vivo and as tumor cell lines grown in vitro. In addition, the cancer cells either overexpressed the tumour-suppressor gene product p53 or harboured human papilloma virus 16/18 (HPV). The TIL were expanded in vitro in the presence of interleukin-2, immobilised anti-CD3 mAb and soluble anti-CD28 mAb. Expanded TIL cultures contained both CD4+and CD8+T cells, but generally contained few CD56+CD3-cells of the natural killer (NK) phenotype. CD8+T cells dominated the individual TIL cultures from five of the six patients and showed significant autologous tumour cell lysis. In TIL cultures derived from four of these tumour-reactive TIL cultures, killing could be partially blocked by an anti-MHC class I mAb. TIL cultures reacting with autologous tumour cells also showed strong TCR/CD3-redirected cytotoxicity when assayed against hybridoma cells expressing anti-TCR/CD3 mAb as well as natural-killer(NK)-like activity. A number of TIL cultures devoid of autologous tumour cell lysis were capable of lysing the natural-killer(NK)-sensitive K562 cell line suggesting that the SCCHN cells themselves are resistant to NK-like lysis. In conclusion, TIL cultures from head and neck carcinomas contain T cells which, upon expansion in vitro, can lyse autologous tumour cells in a MHC-class-I-restricted fashion. Thus, the results of the present study document that carcinomas of the head and neck in some patients are infiltrated by cytotoxic T cell precursors potentially capable of rejecting the autologous tumour.

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References

  1. Battifora H (1991) Assessment of antigen damage in immunohistochemistry. Am J Clin Pathol 96:669

    PubMed  Google Scholar 

  2. Beun G, Velde C, Fleuren G (1994) T-cell based cancer immunotherapy: direct or redirected tumour-cell recognition? Immunol Today 15:11

    PubMed  Google Scholar 

  3. Boes B, Hengel H, Ruppert T, Multhaup G, Koszinowski U, Kloetzel P (1994) Interferon gamma stimulation modulates the proteolytic activity and cleavage site preference of 20S mouse proteasomes. J Exp Med 179:901

    PubMed  Google Scholar 

  4. Böheim K, Denz H, Böheim C, Glassl H, Huber H (1987) An immunohistologic study of the distribution and status of activation of head and neck tumour infiltrating leukocytes. Arch Otorhinolaryngol 244:127

    PubMed  Google Scholar 

  5. Boon T, Cerottini J, Eynde BV, Bruggen P, Pel AV (1994) Tumour antigens recognized by T lymphocytes. Annu Rev Immunol 12:337

    PubMed  Google Scholar 

  6. Brachman D, Graves D, Vokes E, Beckett, Haraf D, Montag A, Dunphy E, Mick R, Yandell D, Weichselbaum R (1992) Occurrence of p53 gene deletions and human papilloma virus infection in human head and neck cancer. Cancer Res 52:4832

    PubMed  Google Scholar 

  7. Brooks C, Urdal D, Henney C (1983) Lymphokine-driven “differentiation” of cytotoxic T-cell clones into cells with NK-like specificity: correlations with display of membrane macromolecules. Immunol Rev 72:42

    Google Scholar 

  8. Chikamatsu K, Eura M, Matsuoka H, Murakami H, Fukiage T, Ishikawa T (1994) The role of major histocompatibility complex expression on head and neck cancer cells in the induction of autologous cytotoxic T lymphocytes. Cancer Immunol Immunother 38:358

    PubMed  Google Scholar 

  9. Chikamatsu K, Eura M, Nakano K, Kanzaki Y, Matsuoka H, Masuyama K, Ishikawa T (1994) Analysis of T cell receptor variability in fresh tumour-infiltrating lymphocytes from human head and neck cancer. Jpn J Cancer Res 85:626

    PubMed  Google Scholar 

  10. Coulie P, Weynants P, Lehmann F, Herman J, Brichard V, Wölfel T, Pel Av, Plaen ED, Brasseur F, Boon T (1993) Genes coding for tumour antigens recognized by human cytolytic T lymphocytes. J Immunother 14:104

    PubMed  Google Scholar 

  11. Eura M, Chikamatsu K, Ogi K, Nakano K, Masuyama K, Ishikawa T (1995) Expression of genes MAGE-1,-2, and 3 by human maxillary carcinoma cells. Anticancer Res 14:1

    Google Scholar 

  12. Field J (1992) Oncogens and tumour-supressor genes in squamous cell carcinoma of the head and neck. Oral Oncol Eur Cancer 28B:67

    Google Scholar 

  13. Flens M, Mulder W, Bril H, Flier M, Scheper R, Lier R (1993) Efficient expansion of tumour-infiltrating lymphocytes from solid tumours by stimulation with combined CD3 and CD28 monoclonal antibodies. Cancer Immunol Immunother 37:323

    PubMed  Google Scholar 

  14. Fukushima K, Ogura H, Watanabe S, Yabe Y, Masuda Y (1994) Human papillomavirus type 16 DNA detected by the polymerase chain reaction in non-cancer tissues of the head and neck. Eur Arch Otorhinolaryngol 251:109

    PubMed  Google Scholar 

  15. Gallo O, Libonati G, Gallina E, Fini-Storchi O, Giannini A, Urso C, Bondi R (1991) Langerhans cells related to prognosis in patients with laryngeal carcinoma. Arch Otolaryngol Head Neck Surg 117:1007

    PubMed  Google Scholar 

  16. Geisler C, Plesner T, Pallesen G, Skjødt K, Ødum N, Larsen J (1988) Characterization and expression of the human T cell receptor-T3 complex by monoclonal antibody F101.01. Scand J Immunol 27:685

    PubMed  Google Scholar 

  17. Gervois N, Heuze F, Diez E, Jotereau F (1990) Selective expansion of a specific anti-tumour CD8+cytotoxic T lymphocyte clone in bulk culture of tumour-infiltrating lymphocytes from a melanoma patient: cytotoxic activity and T cell receptor rearrangements. Eur J Immunol 20:825

    PubMed  Google Scholar 

  18. Guo M, Rabin B, Johnson J, Paradis I (1987) Lymphocyte phenotypes at tumour margins in patients with head and neck cancer. Head Neck Surg 9:265

    PubMed  Google Scholar 

  19. Hald J, Rasmussen N, Claesson M (1994) In vivo infiltration of mononuclear cells in squamous cell carcinoma of the head neck correlates with the ability to expand tumour-infiltrating T cells in vitro and with the expression of MHC class I antigens on tumours cells. Cancer Immunol Immunother 39:383

    PubMed  Google Scholar 

  20. Hall P, Lane D (1994) p53 in tumour pathology: can we trust immunohistochemitry. J Pathol 172:1

    PubMed  Google Scholar 

  21. Harris D, Jaso-Friedmann L, Evans D (1993) A novel target cell antigen involved in the NK-like lytic activity of antigen-specific cytotoxic T lymphocytes. Immunol Lett 38:11

    PubMed  Google Scholar 

  22. Hiratsuka H, Imamura M, Ishii Y, Kohama G, Kikuchi K (1984) Immunohistologic detection of lymphocyte subpopulations infiltrating human oral cancer with special reference to its clinical significance. Cancer 53:2456

    PubMed  Google Scholar 

  23. Kawakami Y, Eliyahu S, Jennings C, Sakaguchi K, Kang X, Southwood S, Robbins P, Sette A, Appella E, Rosenberg S (1995) Recognition of multiple epitopes in the human melanoma antigen gp100 by tumour-infiltrating lymphocytes associated with in vivo tumour regression. J Immunol 154:3961

    PubMed  Google Scholar 

  24. Knudson A (1993) Genetics of tumours of head and neck. Arch Otolaryngol Head Neck Surg 119:735

    PubMed  Google Scholar 

  25. Lazarus P, Garewal H, Sciubba J, Zwiebel N, Calcagnotto A, Fair A, Schaefer S, Richie J (1995) A low incidence of p53 mutations in pre-malignant lesions of the oral cavity from non-tobacco users. Int J Cancer 60:458

    PubMed  Google Scholar 

  26. Liavaag P, Johannessen A, Nilsen R, Jonsson R (1994) Analysis of T cell receptor expressing lymphocytes infiltrating squamous cell carcinomas of the upper aerodigestive tract. Eur Arch Otorhinolaryngol 251:452

    PubMed  Google Scholar 

  27. Nees M, Homann N, Discher H, Andl T, Enders C, Herold-Mende C, Schuhmann A, Bosch F (1993) Expression of mutated p53 occurs in tumour-distant epithelia of head and neck cancer patients: A possible molecular basis for development of multiple tumours. Cancer Res 53:4189

    PubMed  Google Scholar 

  28. Pavelic Z, Portugal L, Gootee M, Stambrook P, Smith C, Mugge R, Wilson K, Buncher R, Li Y, McDonald J, Gluckman J (1993) Retrieval of p53 protein in paraffin-embedded head and neck tumour tissues. Arch Otolaryngol Head Neck Surg 119:1206

    PubMed  Google Scholar 

  29. Rabin B, Johnson J, Claassen D (1984) Identification of subsets of lymphocytes infiltrating head and neck tumour tissue: a preliminary report. Laryngoscope 94:688

    PubMed  Google Scholar 

  30. Salgaller M, Weber J, Koenig S, Yannelli J, Rosenberg S (1994) Generation of specific anti-melanoma reactivity by stimulation of human tumour-infiltrating lymphocytes with MAGE-1 synthetic peptide. Cancer Immunol Immunother 39:105

    PubMed  Google Scholar 

  31. Sato T, Okubo M, Wada Y, Sato N, Kikuchi K (1989) Identification of a human T cell clone with the cytotoxic T lymphocyte and natural killer-like cytotoxic function against autologous mammary carcinoma and K562 line. Jpn J Cancer Res 80:655

    PubMed  Google Scholar 

  32. Slingluff C, Cox A, Henderson R, Hunt D, Engelhard V (1993) Recognition of human melanoma cells by HLA-A2.1-restricted cytotoxic T lymphocytes is mediated by at least six shared peptide epitopes. J Immunol 150:2955

    PubMed  Google Scholar 

  33. Snyderman C, Heo D, Chen K, Whiteside T, Johnson J (1989) T-cell markers in tumour-infiltrating lymphocytes of head and neck cancer. Head Neck 11:331

    PubMed  Google Scholar 

  34. Stevens E, Jacknin L, Robbins P, Kawakami Y, Gamil M, Rosenberg S, Yannelli J (1995) Generation of tumour-specific CTLs from melanoma patients by using peripheral blood stimulated with allogeneic melanoma tumour cell lines. J Immunol 154:762

    PubMed  Google Scholar 

  35. Tomkins P, Ward G, Morris A (1987) Role of interferon-gamma in T-cell responses to semliki forest virus-infected murine brain cells. Immunology 63:355

    Google Scholar 

  36. Townsend A, Bodmer H (1989) Antigen recognition by class Irestricted T lymphocytes. Annu Rev Immunol 7:601

    PubMed  Google Scholar 

  37. UICC (1987) International Union against Cancer. INM classification of malignant tumours. Springer, Berlin Heidelberg New York

    Google Scholar 

  38. White LA, Keane RW, SR Whittemore (1994) Differentiation of an immortal CNS neuronal cell line decreases their susceptibility to cytotoxic T cell lysis in vitro. J Neuroimmunol 49:135

    PubMed  Google Scholar 

  39. Wiedenfeld E, Fernandez-Vina M, Berzofsky J, Minna J, Carbone D (1994) Evidence for selection against human lung cancer bearing p53 missense mutations which occur within the HLA-A*0201 peptide consensus motif. Cancer Res 54:117

    Google Scholar 

  40. Wolf G, Hudson J, Peterson K, Miller H, McClatchey K (1986) Lymphocyte subpopulations infiltrating squamous carcinomas of head and neck: correlations with extent of tumour and prognosis. Otolaryngol Head Neck Surg 95:142

    PubMed  Google Scholar 

  41. Yasumura S, Hirabayashi H, Schwartz D, Toso J, Johnson J, Herberman R, Whiteside T (1993) Human cytotoxic T-cell lines with restricted specificity for squamous cell carcinoma of head and neck. Cancer Res 53:1461

    PubMed  Google Scholar 

  42. Yedwell J, Bennink J, Eager K, Ricciardi R (1988) CTL recognition of adenovirus-transformed cells infected with in fluenza virus: lysis by anti-influenza CTL Parallels adenovirus-12-induced suppression of class I MHC molecules. Virology 162:236

    PubMed  Google Scholar 

  43. Yeudall W (1992) Human papillomaviruses and oral neoplasia. Oral Oncol Eur J Cancer 28:61

    Google Scholar 

  44. Yoshino I, Peoples G, Goedegebuure P, Maziarz R, Eberlein T (1994) Association of HER2/neu expression with sensitivity to tumour-specific CTL in human ovarian cancer. J Immunol 152:2393

    PubMed  Google Scholar 

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Hald, J., Rasmussen, N. & Claesson, M.H. Tumour-infiltrating lymphocytes mediate lysis of autologous squamous cell carcinomas of the head and neck. Cancer Immunol Immunother 41, 243–250 (1995). https://doi.org/10.1007/BF01516999

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  • DOI: https://doi.org/10.1007/BF01516999

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