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Increased projection of MHC and tumor antigens in murine B16-BL6 melanoma induced by hydrostatic pressure and chemical crosslinking

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Abstract

The B16-BL6 melanoma, like most spontaneously arising tumors, is poorly immunogenic and expresses low levels of major histocompatibility complex (MHC) antigens. Treatment of cells of this tumor in vitro by hydrostatic pressure in the presence of adenosine 2′,3′-dialdehyde (oxAdo), a membrane-impermeant crosslinker, caused elevated projection of MHC and a specific tumor antigen as demonstrated by flow-cytometric analysis. Maximum projection of both the MHC and the tumor antigens could be reached by application of 1200 atm for 15 min in the presence of 20 mM oxAdo. It is not yet clear whether this passive increase in availability of antigens on the cell surface originated from a dormant pool of antigens in the plasma membrane or from pressure-induced fusion of antigen-rich intracellular organelles (e.g. the endoplasmic reticulum). The immunogenic properties of the antigen-enriched B16-BL6 cells are described in the following paper.

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References

  1. Ashley M, Kotlarski I (1986) In vivo cytotoxic responses induced by allogeneic normal and neoplastic cells in mice: relative lack of immunogenicity of B16 melanoma cells. Cell Immunol 1: 157

    Google Scholar 

  2. De Baestalier P, Katzav S, Gorelik E, Feldman M, Segal S (1980) Differential expression of H-2 gene products in tumor cells is associated with their metastatogenic properties. Nature 288: 179

    Google Scholar 

  3. Doherty P, Knowles B, Wettstein PI (1984) Immunological surveillance of tumors in the context of major histocompatibility complex restriction of T-cell function. Adv Cancer Res 42: 1

    Google Scholar 

  4. Doyle A, Martin WJ, Funa K, Gazdar A, Carney D, Martin SE, Linnoila I, Cuttia F, Mulshine J, Bunn P, Minna J (1985) Markedly decreased expression of class I histocompatibility antigens, proteins, and mRNA in human small cell lung cancer. J Exp Med 161: 1135

    Google Scholar 

  5. Eisenthal A, Shiloni E, Rosenberg SA (1988) Characterization of IL-2 induced murine cells which exhibit ADCC activity. Cell Immunol 115: 257

    Google Scholar 

  6. Emmrich F (1988) Cross-linking of CD4 and CD8 with T-cell receptor complex: quaternary complex formation and T-cell repertoire selection. Immunol Today 9: 296

    Google Scholar 

  7. Festenstein H, Schmidt W (1981) Variation in MHC antigenic profile of tumor cells and its biological effects. Immunol Rev 60: 85

    Google Scholar 

  8. Fidler IJ (1973) Selection of successive tumor lines for metastasis. Nature 242: 148

    Google Scholar 

  9. Gorelik E, Gunji Y, Herberman RB (1988) H-2 antigen expression and sensitivity of BL6 melanoma cells to natural killer cell cytotoxicity. J Immunol 140: 2096

    Google Scholar 

  10. Gorelik E, Jay G, Kwiatkowski B, Herberman RB (1990) Increased sensitivity to MHC-non restricted lysis of BL6 melanoma cells by transfection with class I H-2Kb gene. J Immunol 145: 1621

    Google Scholar 

  11. Greiner JW, Guadagni F, Noguchi P, Pestka S, Colcher D, Fisher PB, Schlom J (1987) Recombinant interferon enhances monoclonal antibody-targeting of carcinoma lesions in vivo (published erratum appears in Science 236: 657, 1987). Science 235: 895

    Google Scholar 

  12. Hart I (1979) The selection and characterization of an invasive variant of the B16 melanoma. Am J Pathol 97: 587

    Google Scholar 

  13. Ho M, Enders JF (1959) An inhibitor of viral activity appearing in infected cell cultures. Proc Natl Acad Sci USA 45: 385

    Google Scholar 

  14. Höglund P, Ljunggren, HG, Kärre K, Jay G (1990) Role of major histocompatibility complex molecules intumor rejection: new insights from studies with synthetic peptides and transgenic mice. Immunol Res 9: 298

    Google Scholar 

  15. Holden CA, Sanderson AR, McDonald DM (1983) Absence of human leukocyte antigens in skin tumors and some cutaneous appendages: evidence using monoclonal antibodies. J Am Acad Dermatol 9: 867

    Google Scholar 

  16. Hui K, Grosveld F, Festenstein H (1984) Rejection of transplantable AKR leukemia cells followed by MHC-mediated cell transformation. Nature 311: 750

    Google Scholar 

  17. Jones EA, Bodmer WF (1980) Lack of expression of HLA antigens on choriocarcinoma cell lines. Tissue Antigens 16: 195

    Google Scholar 

  18. Klein J (1975) Biology of the mouse histocompatibility-2 complex. Springer, Berlin Heidelberg New York

    Google Scholar 

  19. Lafreniere R, Rosenberg SA (1986) A novel approach to the generation and identification of experimental hepatic metastases in a murine model. JNCI 76: 309

    Google Scholar 

  20. Lampson LA, Fischer CA, Whelan JP (1983) Striking paucity of HLA-A, B, C and β2-microglobulin on human neuroblastoma cell lines. J Immunol 130: 2471

    Google Scholar 

  21. Leong PLS, Muller J, Yetter RA, Gorelik E, Takami T, Hearing VJ (1988) Expression and modulation of a retrovirus-associated antigen by murine melanoma cells. Cancer Res 48: 4954

    Google Scholar 

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

    Google Scholar 

  23. Mulé JJ, Shu S, Schwarz SL, Rosenberg SA (1984) Adoptive immunotherapy of established pulmonary metastases with LAK cells and recombinant IL-2. Science 225: 1487

    Google Scholar 

  24. Mulé JJ, Yang JC, Lafreniere R, Shu S, Rosenberg SA (1987) Identification of cellular mechanisms operational in vivo during the regression of established pulmonary metastases by the systemic administration of high-dose recombinant interleukin-2. J Immunol 139: 285

    Google Scholar 

  25. Muller CP, Stephany DA, Shinitzky M, Wunderlich JR (1983) Changes in cell-surface expression of MHC and Thy 1.2 determinants following treatment with lipid modulating agents. J Immunol 131: 1356

    Google Scholar 

  26. Prager MD, Baechtel SF (1973) Methods for modification of cancer cells to enhance their antigenicity. Methods Cancer Res 9: 339

    Google Scholar 

  27. Ramakrishna V, Shinitzky M (1991) Potentiation of delayed type hypersensitivity response to syngeneic tumors in mice prevaccinated with tumor cells modified by hydrostatic pressure and crosslinking. Cancer Immunol Immunother 33: 1

    Google Scholar 

  28. Richert L, Or A, Shinitzky M (1986) Promotion of tumor antigenicity in EL-4 leukemia cells by hydrostatic pressure Cancer Immunother 22: 119

    Google Scholar 

  29. Sachs DH (1984) The major histocompatibility complex. In: Paul WE (ed) Fundamental immunology. Raven Press, New York, p 303

    Google Scholar 

  30. Sachs DH, Cone JL (1973) A murine B-cell alloantigen determined by gene(s) linked to the major histocompatibility complex. J Exp Med 138: 1289

    Google Scholar 

  31. Sharrow SO, Flaherty L, Sachs DH (1983) Serologic cross-reactivity between class I MHC molecules and an H-2-linked differentiation antigen as detected by monoclonal antibodies. J Exp Med

  32. Shinitzky M (1984) Membrane fluidity in malignancy: adversative and recuperative. Biochim Biophys Acta 738: 251

    Google Scholar 

  33. Shinitzky M, Skornick Y, Haran-Ghera N (1979) Effective tumor immunization induced by cells of elevated membrane-lipid microviscosity. Proc Natl Acad Sci USA 76: 5313

    Google Scholar 

  34. Skornick Y, Danciger E, Rozin RR, Shinitzky M (1981) Positive skin tests with autologous tumor cells of increased membrane viscosity: first report. Cancer Immunol Immunother 11: 93

    Google Scholar 

  35. Skornick Y, Dresdale AR, Sindelar WF (1983) Induction of delayed hypersensitivity reactions in cancer patients by cholesteryl hemisuccinate treated autologous tumor cells. JNCI 70: 465

    Google Scholar 

  36. Skornick Y, Gorelik E, Klausner J, Shinitzky M, Sindelar WF (1984) Inhibition of growth and metastases in mice by immunization with cholesteryl hemisuccinate-enriched tumor cells. Cancer Lett 25: 153

    Google Scholar 

  37. Skornick Y, Kurman CC, Sindelar WF (1984) Active immunization of hamsters against pancreatic carcinoma with lipid treated cells or their shed antigens. Cancer Res 44: 946

    Google Scholar 

  38. Skornick Y, Rong GH, Sindelar WF, Richert L, Klausner JM, Rozin RR, Shinitzky M (1986) Active immunotherapy of human solid tumor with autologous cells treated with cholesteryl hemisuccinate — a phase I study. Cancer 58: 650

    Google Scholar 

  39. Tanaka K, Isselbacher KJ, Khoury G, Jay G (1985) Reversal of oncogenesis by the expression of major histocompatibility class I gene. Science 228: 26

    Google Scholar 

  40. Tanaka K, Gorelik E, Watanabe M, Hozumi N, Jay G (1988) Rejection of B16 melanoma induced by expression of a transfected major histocompatibility complex class I gene. Mol Cell Biol 8: 1857

    Google Scholar 

  41. Van den Eynde B, Hainaut P, Hérin M, Knuth A, Lemoine C, Weynants P, van der Bruggen P, Fauchet R, Boon T (1989) Presence on a human melanoma of multiple antigens recognized by autologous CTL. Int J Cancer 44: 634

    Google Scholar 

  42. Wallich R, Bulbuc N, Hammerling GJ, Katzav S, Segal S, Feldman M (1985) Abrogation of metastatic properties of tumor cells by de novo expression of H-2K antigen following H-2 gene transfection. Nature 315: 301

    Google Scholar 

  43. Weber JS, Rosenberg SA (1988) Modulation of murine tumor major histocompatibility antigens by cytokines in vivo and in vitro. Cancer Res 48: 5818

    Google Scholar 

  44. Weber JS, Rosenberg SA (1990) Effects of murine class I major histocompatibility complex expression on antitumor activity of tumor infiltrating lymphocytes. JNCI 82: 755

    Google Scholar 

  45. Weber JS, Jay G, Tanaka K, Rosenberg SA (1987) Immunotherapy of a murine tumor with interleukin 2. Increased sensitivity after MHC class I gene transfection. J Exp Med 166: 1716

    Google Scholar 

  46. Zinkernagel RM, Doherty PC (1979) MHC-restricted 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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Ramakrishna, V., Eisenthal, A., Skornick, Y. et al. Increased projection of MHC and tumor antigens in murine B16-BL6 melanoma induced by hydrostatic pressure and chemical crosslinking. Cancer Immunol Immunother 36, 293–299 (1993). https://doi.org/10.1007/BF01741167

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  • DOI: https://doi.org/10.1007/BF01741167

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