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Specific immune recognition of autologous tumor by lymphocytes infiltrating colon carcinomas: Analysis by cytokine secretion

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Summary

Tumor-infiltrating lymphocytes (TIL) were grown in the presence of interleukin-2 from 19 colon carcinoma specimens, including 1 primary lesion and 18 metastatic lesions. These cultures showed a median proliferation of 606-fold (range 13-fold to 28 000-fold) over 49 culture days (range 26–76 days). By phenotype, mature cultures were 69%–99% CD3+ (mean 93%) and contained mixed populations of CD4+ and CD8+ cells (CD4>CD8 in 10 of 19 cultures). Fresh cryopreserved colon tumors were not lysed by autologous TIL in short-term51Cr-release assays, and were poorly lysed by lymphokine-activated killer cells. Ten TIL cultures were assayed for cytokine secretion in response to autologous and allogeneic tumors during a 6- to 24-h coincubation. Culture supernatants were tested by ELISA for the presence of granulocyte/macrophage-colony-stimulating factor, interferon γ, and tumor necrosis factor α. Of 10 TIL, 4 secreted at least two of these cytokines specifically in response to autologous and/or HLA-matched fresh allogeneic colon carcinomas, but not to melanomas or HLA-unmatched colon carcinomas. Cytokine secretion was mediated by both CD4+ and CD8+ TIL, and could be inhibited by mAb directed against the appropriate class of MHC antigen. These data provide evidence for specific, MHC-restricted immune recognition of human colon carcinomas by T lymphocytes.

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References

  1. Aebersold P, Hyatt C, Johnson S, Hines K, Korcak L, Sanders M, Lotze MT, Topalian SL, Yang JC, Rosenberg SA (1991) Lysis of autologous melanoma cells by tumor-infiltrating lymphocytes: association with clinical response. JNCI 83: 932

    PubMed  Google Scholar 

  2. Barth RJ Jr, Mulé JJ, Spiess PJ, Rosenberg SA (1991) Interferon-γ and tumor necrosis factor have a role in tumor regressions mediated by murine CD8+ tumor-infiltrating lymphocytes. J Exp Med 173: 647

    PubMed  Google Scholar 

  3. Carrel S, Schmidt-Kessen S, Giuffre L (1985) Recombinant interferon-γ can induce the expression of HLA-A,B,C and tumor associated antigens. Eur J Immunol 15: 118

    PubMed  Google Scholar 

  4. Chong AS-F, Scuderi P, Grimes WJ, Hersh EM (1989) Tumor targets stimulate IL-2 activated killer cells to produce interferon-γ and tumor necrosis factor. J Immunol 142: 2133

    PubMed  Google Scholar 

  5. Grabstein KH, Urdal DL, Tucshinski RJ, Mochizuki R, Price L, Cantrell MA, Gillis S, Conlon PJ (1986) Induction of macrophage tumoricidal activity by granulocyte-macrophage colony stimulating factor. Science 232: 506

    PubMed  Google Scholar 

  6. Hom SS, Topalian SL, Simonis T, Mancini M, Rosenberg SA (1991) Common expression of melanoma tumor-associated antigens recognized by human tumor infiltrating lymphocytes: analysis by human lymphocyte antigen restriction. J Immunother 10: 153

    PubMed  Google Scholar 

  7. Hom SS, Schwartzentruber DS, Rosenberg SA, Topalian SL (1992) Specific release of cytokines by lymphocytes infiltrating human melanomas in response to shared melanoma antigens. J Immunother (in press)

  8. Hutchinson GH, Heinemann D, Symes MO, Williamson CN (1981) Differential immune reactivity of tumor-intrinsic and peripheralblood lymphocytes against autoplastic colorectal carcinoma cells. Br J Cancer 44: 396

    PubMed  Google Scholar 

  9. McDougall CJ, Ngoi SS, Goldman IS, Godwin T, Felix J, DeCosse JJ, Rigas B (1990) Reduced expression of HLA class I and II antigens in colon cancer. Cancer Res 50: 8023

    PubMed  Google Scholar 

  10. Paliard X, Malefijt RDW, Yssel H, Blanchard HD, Chretien I, Abrams J, DeVries J, Spits H (1988) Simultaneous production of IL-2, IL-4, and IFNγ by activated human CD4+ and CD8+ T cell clones. J Immunol 141: 849

    PubMed  Google Scholar 

  11. Pawelec G, Schaudt K, Rehbein A, Busch WF (1989) Differential secretion of tumor necrosis factor-α and granulocyte/macrophage colony-stimulating factors but not interferon-γ from CD4+ compared to CD8+ human T cell clones. Eur J Immunol 19: 197

    PubMed  Google Scholar 

  12. Pfizinmaier K, Scheurich P, Schulter C, Kronke M (1987) Tumor necrosis factor enhances HLA-A,B,C and HLA-DR gene expression in human tumor cells. J Immunol 138: 975

    PubMed  Google Scholar 

  13. Rosenberg SA, Lotze MT, Muul LM, Chang AE, Avis FP, Leitman S, Linehan WM, Robertson CN, Lee R, Rubin JT, Seipp CA, Simpson GC, White DE (1987) A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high dose interleukin 2 alone. N Engl J Med 316: 889

    PubMed  Google Scholar 

  14. Rosenberg SA, Packard BS, Aebersold PM, Solomon D, Topalian SL, Toy ST, Simon P, Lotze MT, Yang JC, Seipp C, Simpson C, Carter C, Bock S, Schwartzentruber DJ, Wei JP, White DE (1988) Use of tumor infiltrating lymphocytes and interleukin 2 in the immunotherapy of patients with metastatic melanoma: a preliminary report. N Engl J Med 319: 1676

    PubMed  Google Scholar 

  15. Schwartzentruber DJ, Topalian SL, Mancini M, Rosenberg SA (1991) Specific release of granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-α, and IFNγ by human tumor infiltrating lymphocytes after autologous tumor stimulation. J Immunol 146: 3674

    PubMed  Google Scholar 

  16. Schwartzentruber DJ, Solomon D, Rosenberg SA, Topalian SL (1992) Characterization of lymphocytes infiltrating human breast cancer: specific immune reactivity can be detected by measuring cytokine secretion. J Immunother 12: 1

    PubMed  Google Scholar 

  17. Schwartzentruber DJ, Stetler-Stevenson MJ, Rosenberg SA, Topalian SL (1992) Specific antitumor immune reactivity by T cells infiltrating human B cell lymphomas (abstract). Proc Am Assoc Cancer Res 33: 309

    Google Scholar 

  18. Shimizu Y, Iwatsuk S, Herberman RB, Whiteside TL (1991) Effects of cytokines on in vitro growth of tumor-infiltrating lymphocytes obtained from human primary and metastatic liver tumors. Cancer Immunol Immunother 32: 280

    PubMed  Google Scholar 

  19. Sugarman BJ, Aggarwal BB, Hass PE, Frgani IS, Palladino MA, Shepard HM (1985) Recombinant TNFα: effects on proliferation of normal and transformed cells in vitro. Science 230: 943

    PubMed  Google Scholar 

  20. Svennevig JL, Lunde OC, Holter J, Bjorgsvik D (1984) Lymphoid infiltration and prognosis in colorectal carcinoma. Br J Cancer 49: 375

    PubMed  Google Scholar 

  21. Topalian SL, Muul LM, Solomon D, Rosenberg SA (1987) Expansion of human tumor infiltrating lymphocytes for use in immunotherapy trials. J Immunol Methods 102: 127

    PubMed  Google Scholar 

  22. Tyring S, Klimpel GR, Fleischmann WR, Baron S (1982) Direct cytolysis by partially purified preparations of immune IFN. Int J Cancer 30: 59

    PubMed  Google Scholar 

  23. Werkmeister JA, Pihl E, Nind APP, Flannery GR, Nairn RC (1979) Immunoreactivity by intrinsic lymphoid cells in colorectal carcinoma. Br J Cancer 40: 839

    PubMed  Google Scholar 

  24. Yoo Y-K, Heo DS, Hata K, Van Thiel DH, Whiteside TL (1990) Tumor-infiltrating lymphocytes from human colon carcinomas: functional and phenotypic characteristics after long-term culture in recombinant interleukin 2. Gastroenterology 98: 259

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Surgery Branch, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Building 10, Room 2B42, 20892, Bethesda, Maryland, USA

    Sophia S. Hom, Steven A. Rosenberg & Suzanne L. Topalian

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  1. Sophia S. Hom
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  2. Steven A. Rosenberg
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  3. Suzanne L. Topalian
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Hom, S.S., Rosenberg, S.A. & Topalian, S.L. Specific immune recognition of autologous tumor by lymphocytes infiltrating colon carcinomas: Analysis by cytokine secretion. Cancer Immunol Immunother 36, 1–8 (1993). https://doi.org/10.1007/BF01789124

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  • DOI: https://doi.org/10.1007/BF01789124

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