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Expression of the adhesion molecule ICAM-1 and major histocompatibility complex class I antigens on human tumor cells is required for their interaction with autologous lymphocytes in vitro

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Summary

In a group of 30 human tumors, comprising 12 lung, 14 ovarian, 2 breast carcinomas, 1 hypernephroma and 1 mid-gut carcinoid, the expression of major histocompatibility complex (MHC) class I molecules and the intercellular adhesion molecule 1 (ICAM-1, CD54) was found to vary independently. Some tumors expressed both or neither of these molecules. Among 9/13 ICAM-1+ tumors, in which >50% cells reacted with the anti-ICAM-1 monoclonal antibody (mAb) (LB-2), the class I antigen was also detected on >50% of the cells. Only 2 ICAM-1+ tumors were class-I−. In 5/17 cases the tumors were MHC-class-I+ and ICAM-1−. Lymphocytes collected from the blood or from the tumor site were assayed for recognition on the tumor cells in the auto-tumor cytotoxicity test and in mixed lymphocyte tumor cell culture (MLTC). Positive results were obtained only with the MHC-class-I+/ICAM-1+ tumors. In vitro treatment of the tumor cell suspensions with interferon γ and tumor necrosis factor α (TNFα) induced or enhanced the ICAM-1 and/or class I antigen expression in 8/12 cases. Of the tumor samples treated, 8/9 aquired stimulatory capacity and 3/10 became susceptible to lysis by the lymphocytes. In 6/6 MLTC performed with the cytokine-treated tumor cells, cytotoxicity against the autologous tumor was generated. Three of these MLTC lymphocytes also lysed the untreated targets. mAb directed to class I antigens or to ICAM-1 inhibited both the stimulation by and the lysis of tumor cells when confronted with fresh lymphocytes. The cytotoxicity generated in the MLTC was also inhibited. If, however, the cytotoxic function was induced in MLTC containing interleukin-2 (5 U/ml), inhibition was obtained only by pretreatment of the targets with mAb against ICAM-1. The results show thus (a) that the lymphocytes react in vitro with tumor cells only if these express both MHC class I molecules and ICAM-1; (b) that expression of these molecules can be induced by interferon α and TNFα; (c) that cytotoxic effectors generated in the MLTC with cytokine-treated tumors can also act on the untreated tumor cells. The requirement of the two surface moieties for the interaction with lymphocytes was also substantiated by blockade with relevant mAb.

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References

  1. Accolla RS, Sekaly RP, McDonald AP, Corte G, Gross N, Carrel S (1982) Demonstration on the single cell level of the existence of distinct clusters of epitopes in two predefined human Ia molecular subsets. Eur J Immunol 12: 166

    Google Scholar 

  2. Bahn AK, DesMarias CL (1983) Immunohistological characterisation of major histocompatibility antigens and inflammatory cellular infiltrate in human breast cancer. J Natl Cancer Inst 71: 507

    Google Scholar 

  3. Beatty PG, Ledbetter JA, Martin PJ, Price TH, Hansen JA (1983) Definition of a common leukocyte cell-surface antigen (LP 95-150) associated with diverse cell-mediated immune functions. J Immunol 131: 1913

    Google Scholar 

  4. Bierer BE, Peterson A, Takai Y, Greenstein J, Herrmann S, Seed B, Burakoff SJ (1987) Evidence that LFA-3 activates T cells via the CD2 receptor. Fed Proc 46: 1498

    Google Scholar 

  5. Björkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC (1987) The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature 329: 512

    Google Scholar 

  6. Boon T, van Pel A, Uyttenhove C, Marchand M, Lambotte P (1984) Tum− variants and the detection of tumor specific transplantation antigens on spontaneous mouse tumors. Behring Inst Mitt 74: 209

    Google Scholar 

  7. Böyum A (1974) Separation of blood leukocytes, granulocytes and lymphocytes. Tissue Antigens 4: 269

    Google Scholar 

  8. Callagen GN (1985) Products of the major histocompatibility complex on tumor cells. In: Sell S, Reisfeld, RA (eds) Monoclonal antibodies and cancer. Humana Press, Clifton, New Jersey, pp 97–121

    Google Scholar 

  9. Clark EA, Ledbetter JA, Holly RC, Dinndorf PA, Shu G (1986) Polypeptides on human B lymphocytes associated with cell activation. Hum Immunol 16: 100

    Google Scholar 

  10. Clayberger C, Wright A, Medeiros LJ, Koller TD, Link MP, Smith SD, Warnke RA, Krensky AM (1987) Absence of cell surface LFA-1 as a mechanism of escape from immunosurveillance. Lancet II, 533–536

    Google Scholar 

  11. Csiba A, Whitwell HL, Moore M (1984) Distribution of histocompatibility and leucocyte differentiation antigens in normal human colon and in benign and malignant colonic neoplasms, Br J Cancer 50: 699

    Google Scholar 

  12. Daar AS, Fabre JW (1983) The membrane antigens of human colorectal cancer cells: demonstration with monoclonal antibodies of heterogenicity within and between tumours and anomalous expression of HLA-DR. Eur J Cancer Clin Oncol 19: 209

    Google Scholar 

  13. Daar AS, Fuggle SV, Fabre JV, Ting A, Morris PJ (1984) The detailed distribution of HLA-ABC antigens in normal human organs. Transplantation 38: 287

    Google Scholar 

  14. Dougherty GJ, Murdoch S, Hogg N (1988) The function of human intercellular adhesion molecule-1 (ICAM-1) in the generation of immune response. Eur J Immunol 18: 35

    Google Scholar 

  15. Doyle A, Martin WJ, Gazdar A, Carney D, Martin SE, Linnoila I, Cuttita F, Mulshine J, Bunn P, Minna J (1985) Markedly decreased expression of class I histocompatibility antigens, protein and m RNA in human small cell lung cancer. J Exp Med 161: 1135

    Google Scholar 

  16. Dustin LM, Springer TA (1988) Lymphocyte function-associated antigen-1 (LFA-1) interaction with intercellular adhesion molecule-1 (ICAM-1) is one of at least three mecanisms for lymphocyte adhesion to cultured endothelial cells. J Cell Biol 107: 321–331

    Google Scholar 

  17. Eisenbach L, Segal S, Feldman M (1983) MHC imbalance and metastatic spread in Lewis lung carcinoma clones. Int J Cancer 32: 113

    Google Scholar 

  18. Elliott BE, Carlow DA, Rodricks AM, Wade A (1989) Perspectives on the role of major histocompatibility antigens in normal and malignant cell development. Adv Cancer Res (in press)

  19. Festenstein H (1987) The biological consequences of altered MHC expression on tumours. Br Med Bull 43: 217

    Google Scholar 

  20. Forman J (1984) T cells, the MHC, and functions. Immunol Rev 81: 203

    Google Scholar 

  21. Garcia-Espejo R, Alonso MC, Solana R, Pera C, Pena J (1986) Expression of HLA molecules on cells from fresh explants of human digestive tract cancer. J Immunogenet 13: 211

    Google Scholar 

  22. Ghosh AK, Moore M, Street AJ, Howat JMT, Schofield PF (1986) Expression of HLA-D subregion products on human colorectal carcinoma. Int J Cancer 38: 159

    Google Scholar 

  23. Hämmerling GJ, Klar D, Katzaw S, Segal S, Feldman M, Wallich R, Hämmerling A (1986) Manipulation of metastasis and tumor growth by transfection with histocompatibility class I antigens. J Immunogenet 13: 153

    Google Scholar 

  24. Hämmerling GJ, Klar D, Pülm W, Momburg F, Moldenhauer G (1987) The influence of major histocompatibility complex class I antigens on tumor growth and metastasis. Biochim Biophys Acta 907: 245

    Google Scholar 

  25. Hirshberg H, Braathen LR, Thorsby E (1982) Antigen presentation by vascular endothelial cell and epidermal Langerhans cells: the role of HLA-DR. Immunol Rev 66: 57

    Google Scholar 

  26. Hynes RO (1987) Integrins: a family of cell surface receptors. Cell 48: 549

    Google Scholar 

  27. Jalkanen S, Reichert RA, Gallatin WM, Bargatze RF, Weissman IL, Butcher EC (1986) Homing receptors and the control of lymphocyte migration. Immunol Rev 91: 39

    Google Scholar 

  28. Julius MH, Simpson E, Herzenberg LA (1974) Rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol 3: 645

    Google Scholar 

  29. Kaba DS, McIntyre BW, Kripke ML, Goodenow RS, Schreiber H, Ananthaswamy HN (1989) Generation of antigenic variants from a non-immunogenic murine tumor cell line by transfection with gene encoding a novel tumor specific transplantation antigen. Cancer Res 49: 38

    Google Scholar 

  30. Kabawat SE, Bast RC Jr, Welch WR, Knapp RC, Bahn AK (1983) Expression of major histocompatibility antigens and nature of inflammatory cellular infiltrate in ovarian neoplasms. Int J Cancer 32: 547

    Google Scholar 

  31. Katzav S, Tartokovsky B, de Baetselier P, Isakov N, Feldman M, Segal S (1983) Role of MHC encoded glycoproteins in tumor dissemination. Transplant Proc 15: 162

    Google Scholar 

  32. Leontsini E, Brown T, Biddison W (1986) Physical and functional association of the T cell receptor and the T3 molecular complex on cytotoxic T cell clones that are differentially inhibitable by anti-T3 antibody. Cell Immunol 102: 21

    Google Scholar 

  33. Makgoba MW, Sanders ME, Ginther Luce GE, Gugel EA, Dustin ML, Springer TA, Shaw S (1988) Functional evidence that intercellular adhesion molecule 1 (ICAM-1) is a ligand for LFA-1-dependent adhesion in T cell mediated cytotoxicity. Eur J Immunol 18: 637

    Google Scholar 

  34. Marlin SD, Springer TA (1987) Purified intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte function-associated antigen-1 (LFA-1). Cell 51: 813

    Google Scholar 

  35. Martz E (1987) LFA-1 and other accessory molecules functioning in adhesions of T and B lymphocytes. Hum Immunol 18: 3

    Google Scholar 

  36. Maryanski JL, Pala P, Cerottini J-Ch, MacDonald HR (1988) Antigen recognition by H-2 restricted cytolytic T lymphocytes: inhibition of cytolysis by anti-CD8 monoclonal antybodies depends upon both concentration and primary sequence of peptide antigen. Eur J Immunol 18: 1863

    Google Scholar 

  37. Möller P, Herrman P, Moldenhauer G, Momburg F (1987) Defective expression of MHC class I antigens is frequent in B cell lymphomas of high-grade malignancy. Int J Cancer 40: 32

    Google Scholar 

  38. Momburg F, Möller P, Moldenhauer C, Hämmerling GJ (1986) Loss of HLA-ABC in colorectal carcinoma is related to the degree of de-differentiation. J Immunogent 13: 195

    Google Scholar 

  39. Momburg F, Ziegler A, Harprecht J, Möller P, Moldenhauer G, Hämmerling GJ (1989) Selective loss of HLA-A and HLA-B antigen expression in colon carcinoma. J Immunol 142: 352

    Google Scholar 

  40. Natali PG, Bigotti A, Nicorta MR, Viotra M, Manfredi D, Ferrone S (1984) Distribution of human class I (HLA-ABC) histocompatibility antigens in normal and malignant tissues of non-lymphoid origin. Cancer Res 44: 4679

    Google Scholar 

  41. Ortho-mune monoclonal antibodies product monograph. 3 (1982) Ortho Diagnostic System, Raritan

  42. Patarroyo M, Makgoba W (1989) Leukocyte adhesion to cells. Molecular basis, physiological relevance and abnormalities. Scand J Immunol 30: 129

    Google Scholar 

  43. Perez M, Cabrera T, Lopez-Nevot MA, Gomez M, Peran F, Ruiz-Cabello F, Garrido F (1986) Heterogenicity of the expression of class I and class II HLA antigens in human breast carcinoma. J Immunogenet 13: 247

    Google Scholar 

  44. Pircher H, Groscurth P, Baumhutter S, Aguet M, Zinkernagel RM, Hengartner H (1986) A monoclonal antibody against altered LFA-1 induces proliferation and lymphokine release of cloned T cells. Eur J Immunol 16: 172

    Google Scholar 

  45. Rothlein R, Dustin ML, Marlin SD, Springer TA (1986) A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1. J Immunol 137: 1270

    Google Scholar 

  46. Rothlein R, Czajkowski M, O'neill MM, Marlin SD, Mainofli E, Merluzzi VJ (1988) Induction of intercellular adhesion molecule-1 on primary and continuous cell lines by pro-inflammatory cytokines. J Immunol 141: 1665

    Google Scholar 

  47. Ruiter DJ, Bergman W, Welvaart K, Scheffer E, van Vloten WA, Russo C, Ferrone S (1984) Immunohistochemical analysis of malignant melanomas and nevocellular nevi with monoclonal antibodies to distinct monomorphic determinant of HLA antigens. Cancer Res 14: 3930

    Google Scholar 

  48. Shackelford DA, Kaufman JF, Korman AJ, Strominger JL (1982) HLA-DR antigens: Structure, separation of subpopulations, gene cloning and function. Immunol Rev 66: 133

    Google Scholar 

  49. Spits J, Van Schooten W, Keiser H, Van Seventer G, Van de Rijn M, Terhorst C, De Vries DE (1986) Alloantigen recognition is preceded by nonspecific adhesion of cytotoxic T cells and target cells. Science 232: 403

    Google Scholar 

  50. Springer TA, Davignon D, Ho MK, Kürzinger K, Martz E, Sanchez-Madrid F (1982) LFA-1 and Lyt-2,3 molecules associated with T lymphocyte-mediated killing, and Mac-1, an LFA-1 homologue associated with complemen function. Immunol Rev 68: 111

    Google Scholar 

  51. Stötter H, Wiebke EA, Tomita S, Belldegrun A, Topalain S, Rosenberg SA, Lotze MT (1989) Cytokines alter target cell susceptibility to lysis. J Immunol 142: 1767

    Google Scholar 

  52. Timonen T, Saksela E, Ranki A, Häyry P (1979) Fractionation, morphological and functional characterization of effector cells responsible for human natural killer activity against cell-line targets. Cell Immunol 48: 133

    Google Scholar 

  53. Vánky F (1986) Membrane structures involved in auto-tumor recognition. Biochim Biophys Acta 865

  54. Vánky F, Klein E (1989) Autor-tumor lysis by blood lymphocytes in vitro. Strongly activated lymphocytes lack specificity. Cancer Immunol Immunother 29: 125

    Google Scholar 

  55. Vánky F, Klein E, Willems J (1985) DR antigens expressed on tumor cells do not contribute to the blastogenic response of autologous T cells. Cancer Immunol Immunother 19: 219

    Google Scholar 

  56. Vánky F, Klein E, Willems J, Böök K, Ivert T, Péterffy A, Nilsonne U, Kreicbergs A, Aparisi T (1986) Lysis of autologous tumor cells by blood lymphocytes tested at the time of surgery. Correlation with the postsurgical clinical course. Cancer Immunol Immunother 21: 69

    Google Scholar 

  57. Vánky F, Klein E, Willems J, Böök K, Ivert T, Péterffy A (1987) Recognition of autologous tumour cells by blood lymphocytes in patients with lung cancer. In: Byers VS, Baldwin RW (eds) Immunology of malignant diseases. MTP Press Ltd, Lancaster, pp 105–128

    Google Scholar 

  58. Vánky F, Roberts T, Klein E, Willems J (1987) Auto-tumor immunity in patients with solid tumors: participation of CD3 complex and MHC class I antigens in the lytic interaction. Immunol Lett 16: 21

    Google Scholar 

  59. Vánky F, Stuber G, Willems J, Sjöwall K, Larsson B, Böök K, Ivert T, Péterffy A, Klein E (1988) Importance of MHC antigen expression on solid tumors in the in vitro interaction with autologous blood lymphocytes. Cancer Immunol Immunother 27: 213

    Google Scholar 

  60. Vánky F, Stuber G, Rotstein S, Klein E (1989) Auto-tumor recognition following in vitro induction of MHC antigen expression on solid tumors: stimulation of lymphocytes and generation of cytotoxicity against the original MHC-antigennegative tumor cells. Cancer Immunol Immunother 28: 17

    Google Scholar 

  61. Vogetseder W, Feitinger H, Schulz TF, Schwaeble W, Tabaczewski P, Mitterer M, Böck G, Marth C, Dapunt O, Mikuz G, Dierich MP (1989) Expression of 7F7-antigen, a human adhesion molecule identical to intercellular adhesion molecule-1 (ICAM-1) in human carcinomas and their stromal fibroblasts. Int J Cancer 43: 768

    Google Scholar 

  62. Vollger LW, Tuck DT, Springer TA, Haynes BF, Singer KH (1987) Thymocyte binding to human thymic epithelial cells is inhibited by monoclonal antibodies to CD2 and LFA-3 antigens. J Immunol 138: 358

    Google Scholar 

  63. Whitwell HL, Hughes HPA, Moore M, Ahmed A (1984) Expression of major histocompatibility antigens and leukocyte infiltration in benign and malignant human breast disease. Br J Cancer 49: 161

    Google Scholar 

  64. Zinkernagel RM, Doherty PV (1979) MHC cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T cell restriction-specificity, function and responsiveness. Adv Immunol 27: 51

    Google Scholar 

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Authors and Affiliations

  1. Department of Tumor Biology, Karolinska Institute, S-104 01, Stockholm, Sweden

    F. Vánky, P. Wang & E. Klein

  2. Radiumhemmet, Karolinska Hospital, S-104 01, Stockholm, Sweden

    F. Vánky & P. Wang

  3. Department of Immunology, Karolinska Institute, 104 01, Stockholm, Sweden

    M. Patarroyo

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Vánky, F., Wang, P., Patarroyo, M. et al. Expression of the adhesion molecule ICAM-1 and major histocompatibility complex class I antigens on human tumor cells is required for their interaction with autologous lymphocytes in vitro. Cancer Immunol Immunother 31, 19–27 (1990). https://doi.org/10.1007/BF01742491

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