Decreased tumor surveillance in perforin-deficient mice

doi:10.1084/jem.184.5.1781

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Decreased tumor surveillance in perforin-deficient mice

ME van den Broek, D Kagi, F Ossendorp, R Toes, S Vamvakas, WK Lutz, CJ Melief, RM Zinkernagel and H Hengartner
Institute of Experimental Immunology, University of Zurich, Switzerland.

Immune surveillance against tumors usually depends on T cell recognition of tumor antigens presented by major histocompatibility complex (MHC) molecules, whereas MHC class I- tumors may be controlled by natural killer (NK) cells. Perforin-dependent cytotoxicity is a major effector function of CD8+ MHC class I-restricted T cells and of NK cells. Here, we used perforin-deficient C57BL/6 (PKO) mice to study involvement of perforin and Fas ligand in tumor surveillance in vivo. We induced tumors in PKO and normal C57BL/6 mice by (a) injection of different syngeneic tumor cell lines of different tissue origin in naive and primed mice; (b) administration of the chemical carcinogens methylcholanthrene (MCA) or 12-O-tetradecanoylphorbol-13-acetate (TPA) plus 7,12-dimethylbenzanthracene (DMBA), or (c) by injection of acutely oncogenic Moloney sarcoma virus. The first set of models analyzes the defense against a tumor load given at once, whereas the last two sets give information on immune defense against tumors at the very moment of their generation. Most of the tumor cell lines tested were eliminated 10-100-fold better by C57BL/6 mice in an unprimed situation; after priming, the differences were more pronounced. Lymphoma cells transfected with Fas were controlled 10-fold better by PKO and C57BL/6 mice when compared to untransfected control cells, indicating some role for FasL in tumor control. MCA-induced tumors arose more rapidly and with a higher incidence in PKO mice compared to C57BL/6 or CD8- deficient mice. DMBA+TPA-induced skin papillomas arose with similar high incidence and comparable kinetics in both mouse strains. C57BL/6 and PKO mice have a similar incidence of Moloney murine sarcoma and leukemia virus-induced sarcomas, but tumors are larger and regression is retarded in PKO mice. Thus, perforin-dependent cytotoxicity is not only a crucial mechanism of both cytotoxic T lymphocyte- and NK- dependent resistance to injected tumor cell lines, but also operates during viral and chemical carcinogenesis in vivo. Experiments addressing the role of Fas-dependent cytotoxicity by studying resistance to tumor cell lines that were stably transfected with Fas neither provided evidence for a major role of Fas nor excluded a minor contribution of Fas in tumor surveillance.
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Caldwell, S. A., Ryan, M. H., McDuffie, E., Abrams, S. I. (2003). The Fas/Fas Ligand Pathway Is Important for Optimal Tumor Regression in a Mouse Model of CTL Adoptive Immunotherapy of Experimental CMS4 Lung Metastases. J. Immunol. 171: 2402-2412 [Abstract] [Full Text]
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Krishnan, L., Sad, S., Patel, G. B., Sprott, G. D. (2003). Archaeosomes Induce Enhanced Cytotoxic T Lymphocyte Responses to Entrapped Soluble Protein in the Absence of Interleukin 12 and Protect against Tumor Challenge. Cancer Res. 63: 2526-2534 [Abstract] [Full Text]
Gitelson, E., Hammond, C., Mena, J., Lorenzo, M., Buckstein, R., Berinstein, N. L., Imrie, K., Spaner, D. E. (2003). Chronic Lymphocytic Leukemia-reactive T Cells during Disease Progression and after Autologous Tumor Cell Vaccines. Clin. Cancer Res. 9: 1656-1665 [Abstract] [Full Text]
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Bose, A., Inoue, Y., Kokko, K. E., Lakkis, F. G. (2003). Cutting Edge: Perforin Down-Regulates CD4 and CD8 T Cell-Mediated Immune Responses to a Transplanted Organ. J. Immunol. 170: 1611-1614 [Abstract] [Full Text]
Wulffraat, N. M., Rijkers, G. T., Elst, E., Brooimans, R., Kuis, W. (2003). Reduced perforin expression in systemic juvenile idiopathic arthritis is restored by autologous stem-cell transplantation. Rheumatology (Oxford) 42: 375-379 [Abstract] [Full Text]
Hayakawa, Y., Kelly, J. M., Westwood, J. A., Darcy, P. K., Diefenbach, A., Raulet, D., Smyth, M. J. (2002). Cutting Edge: Tumor Rejection Mediated by NKG2D Receptor-Ligand Interaction Is Dependent upon Perforin. J. Immunol. 169: 5377-5381 [Abstract] [Full Text]
San Mateo, L. R., Chua, M. M., Weiss, S. R., Shen, H. (2002). Perforin-Mediated CTL Cytolysis Counteracts Direct Cell-Cell Spread of Listeria monocytogenes. J. Immunol. 169: 5202-5208 [Abstract] [Full Text]
Chiu, P. P. L., Ivakine, E., Mortin-Toth, S., Danska, J. S. (2002). Susceptibility to Lymphoid Neoplasia in Immunodeficient Strains of Nonobese Diabetic Mice. Cancer Res. 62: 5828-5834 [Abstract] [Full Text]
Schepers, K., Toebes, M., Sotthewes, G., Vyth-Dreese, F. A., Dellemijn, T. A. M., Melief, C. J. M., Ossendorp, F., Schumacher, T. N. M. (2002). Differential Kinetics of Antigen-Specific CD4+ and CD8+ T Cell Responses in the Regression of Retrovirus-Induced Sarcomas. J. Immunol. 169: 3191-3199 [Abstract] [Full Text]
Tsung, K., Dolan, J. P., Tsung, Y. L., Norton, J. A. (2002). Macrophages as Effector Cells in Interleukin 12-induced T Cell-dependent Tumor Rejection. Cancer Res. 62: 5069-5075 [Abstract] [Full Text]
Street, S. E.A., Trapani, J. A., MacGregor, D., Smyth, M. J. (2002). Suppression of Lymphoma and Epithelial Malignancies Effected by Interferon {gamma}. J. Exp. Med. 196: 129-134 [Abstract] [Full Text]
Qin, Z., Kim, H.-J., Hemme, J., Blankenstein, T. (2002). Inhibition of Methylcholanthrene-induced Carcinogenesis by an Interferon {gamma} Receptor-dependent Foreign Body Reaction. J. Exp. Med. 195: 1479-1490 [Abstract] [Full Text]
Igney, F. H., Krammer, P. H. (2002). Immune escape of tumors: apoptosis resistance and tumor counterattack. J. Leukoc. Biol. 71: 907-920 [Abstract] [Full Text]
Seki, N., Brooks, A. D., Carter, C. R. D., Back, T. C., Parsoneault, E. M., Smyth, M. J., Wiltrout, R. H., Sayers, T. J. (2002). Tumor-Specific CTL Kill Murine Renal Cancer Cells Using Both Perforin and Fas Ligand-Mediated Lysis In Vitro, But Cause Tumor Regression In Vivo in the Absence of Perforin. J. Immunol. 168: 3484-3492 [Abstract] [Full Text]
Takeda, K., Smyth, M. J., Cretney, E., Hayakawa, Y., Kayagaki, N., Yagita, H., Okumura, K. (2002). Critical Role for Tumor Necrosis Factor-related Apoptosis-inducing Ligand in Immune Surveillance Against Tumor Development. J. Exp. Med. 195: 161-169 [Abstract] [Full Text]
Medema, J. P., de Jong, J., Peltenburg, L. T. C., Verdegaal, E. M. E., Gorter, A., Bres, S. A., Franken, K. L. M. C., Hahne, M., Albar, J. P., Melief, C. J. M., Offringa, R. (2001). Blockade of the granzyme B/perforin pathway through overexpression of the serine protease inhibitor PI-9/SPI-6 constitutes a mechanism for immune escape by tumors. Proc. Natl. Acad. Sci. USA 10.1073/pnas.201398198v1 [Abstract] [Full Text]
van Elsas, A., Sutmuller, R. P.M., Hurwitz, A. A., Ziskin, J., Villasenor, J., Medema, J.-P., Overwijk, W. W., Restifo, N. P., Melief, C. J.M., Offringa, R., Allison, J. P. (2001). Elucidating the Autoimmune and Antitumor Effector Mechanisms of a Treatment Based on Cytotoxic T Lymphocyte Antigen-4 Blockade in Combination with a B16 Melanoma Vaccine: Comparison of Prophylaxis and Therapy. J. Exp. Med. 194: 481-490 [Abstract] [Full Text]
Topham, D. J., Cardin, R. C., Christensen, J. P., Brooks, J. W., Belz, G. T., Doherty, P. C. (2001). Perforin and Fas in murine gammaherpesvirus-specific CD8+ T cell control and morbidity. J. Gen. Virol. 82: 1971-1981 [Abstract] [Full Text]
Smyth, M. J., Kelly, J. M., Sutton, V. R., Davis, J. E., Browne, K. A., Sayers, T. J., Trapani, J. A. (2001). Unlocking the secrets of cytotoxic granule proteins. J. Leukoc. Biol. 70: 18-29 [Abstract] [Full Text]
Schmaltz, C., Alpdogan, O., Horndasch, K. J., Muriglan, S. J., Kappel, B. J., Teshima, T., Ferrara, J. L. M., Burakoff, S. J., van den Brink, M. R. M. (2001). Differential use of Fas ligand and perforin cytotoxic pathways by donor T cells in graft-versus-host disease and graft-versus-leukemia effect. Blood 97: 2886-2895 [Abstract] [Full Text]
Smyth, M. J., Crowe, N. Y., Godfrey, D. I. (2001). NK cells and NKT cells collaborate in host protection from methylcholanthrene-induced fibrosarcoma. Int Immunol 13: 459-463 [Abstract] [Full Text]
Behrens, C. K., Igney, F. H., Arnold, B., Moller, P., Krammer, P. H. (2001). CD95 Ligand-Expressing Tumors Are Rejected in Anti-Tumor TCR Transgenic Perforin Knockout Mice. J. Immunol. 166: 3240-3247 [Abstract] [Full Text]
Street, S. E. A., Cretney, E., Smyth, M. J. (2001). Perforin and interferon-{gamma} activities independently control tumor initiation, growth, and metastasis. Blood 97: 192-197 [Abstract] [Full Text]
Peng, L., Krauss, J. C., Plautz, G. E., Mukai, S., Shu, S., Cohen, P. A. (2000). T Cell-Mediated Tumor Rejection Displays Diverse Dependence Upon Perforin and IFN-{gamma} Mechanisms That Cannot Be Predicted From In Vitro T Cell Characteristics. J. Immunol. 165: 7116-7124 [Abstract] [Full Text]
Plautz, G. E., Mukai, S., Cohen, P. A., Shu, S. (2000). Cross-Presentation of Tumor Antigens to Effector T Cells Is Sufficient to Mediate Effective Immunotherapy of Established Intracranial Tumors. J. Immunol. 165: 3656-3662 [Abstract] [Full Text]
Smyth, M. J., Thia, K. Y.T., Street, S. E.A., MacGregor, D., Godfrey, D. I., Trapani, J. A. (2000). Perforin-mediated Cytotoxicity Is Critical for Surveillance of Spontaneous Lymphoma. J. Exp. Med. 192: 755-760 [Abstract] [Full Text]
Rabinovich, B. A., Shannon, J., Su, R.-C., Miller, R. G. (2000). Stress Renders T Cell Blasts Sensitive to Killing by Activated Syngeneic NK Cells. J. Immunol. 165: 2390-2397 [Abstract] [Full Text]
Hsieh, M. H., Korngold, R. (2000). Differential use of FasL- and perforin-mediated cytolytic mechanisms by T-cell subsets involved in graft-versus-myeloid leukemia responses. Blood 96: 1047-1055 [Abstract] [Full Text]
Sayers, T. J., Brooks, A. D., Seki, N., Smyth, M. J., Yagita, H., Blazar, B. R., Malyguine, A. M. (2000). T cell lysis of murine renal cancer: multiple signaling pathways for cell death via Fas. J. Leukoc. Biol. 68: 81-86 [Abstract] [Full Text]
Berthou, C., Bourge, J.-F., Zhang, Y., Soulie, A., Geromin, D., Denizot, Y., Sigaux, F., Sasportes, M. (2000). Interferon-gamma -induced membrane PAF-receptor expression confers tumor cell susceptibility to NK perforin-dependent lysis. Blood 95: 2329-2336 [Abstract] [Full Text]
Rosen, D., Li, J.-H., Keidar, S., Markon, I., Orda, R., Berke, G. (2000). Tumor Immunity in Perforin-Deficient Mice: A Role for CD95 (Fas/APO-1). J. Immunol. 164: 3229-3235 [Abstract] [Full Text]
Smyth, M. J., Thia, K. Y. T., Street, S. E.A., Cretney, E., Trapani, J. A., Taniguchi, M., Kawano, T., Pelikan, S. B., Crowe, N. Y., Godfrey, D. I. (2000). Differential Tumor Surveillance by Natural Killer (NK) and NKT Cells. J. Exp. Med. 191: 661-668 [Abstract] [Full Text]
Zhang, J., Scordi, I., Smyth, M. J., Lichtenheld, M. G. (1999). Interleukin 2 Receptor Signaling Regulates the Perforin Gene through Signal Transducer and Activator of Transcription (Stat)5 Activation of Two Enhancers. J. Exp. Med. 190: 1297-1308 [Abstract] [Full Text]
Fallarino, F., Gajewski, T. F. (1999). Cutting Edge: Differentiation of Antitumor CTL In Vivo Requires Host Expression of Stat1. J. Immunol. 163: 4109-4113 [Abstract] [Full Text]
Winter, H., Hu, H.-M., Urba, W. J., Fox, B. A. (1999). Tumor Regression After Adoptive Transfer of Effector T Cells Is Independent of Perforin or Fas Ligand (APO-1L/CD95L). J. Immunol. 163: 4462-4472 [Abstract] [Full Text]
Medema, J. P., de Jong, J., van Hall, T., Melief, C. J.M., Offringa, R. (1999). Immune Escape of Tumors In Vivo by Expression of Cellular FLICE-inhibitory Protein. J. Exp. Med. 190: 1033-1038 [Abstract] [Full Text]
Podack, E. R. (1999). How to induce involuntary suicide: The need for dipeptidyl peptidase I. Proc. Natl. Acad. Sci. USA 96: 8312-8314 [Full Text]
Smyth, M. J., Thia, K. Y. T., Cretney, E., Kelly, J. M., Snook, M. B., Forbes, C. A., Scalzo, A. A. (1999). Perforin Is a Major Contributor to NK Cell Control of Tumor Metastasis. J. Immunol. 162: 6658-6662 [Abstract] [Full Text]
Kayagaki, N., Yamaguchi, N., Nakayama, M., Eto, H., Okumura, K., Yagita, H. (1999). Type I Interferons (IFNs) Regulate Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) Expression on Human T Cells: A Novel Mechanism for the Antitumor Effects of �Type I IFNs. J. Exp. Med. 189: 1451-1460 [Abstract] [Full Text]
Tsukada, N., Kobata, T., Aizawa, Y., Yagita, H., Okumura, K. (1999). Graft-Versus-Leukemia Effect and Graft-Versus-Host Disease Can Be Differentiated by Cytotoxic Mechanisms in a Murine Model of Allogeneic Bone Marrow Transplantation. Blood 93: 2738-2747 [Abstract] [Full Text]
Kehren, J., Desvignes, C., Krasteva, M., Ducluzeau, M.-T., Assossou, O., Horand, F., Hahne, M., Kagi, D., Kaiserlian, D., Nicolas, J.-F. (1999). Cytotoxicity Is Mandatory for CD8+ T Cell-mediated Contact Hypersensitivity. J. Exp. Med. 189: 779-786 [Abstract] [Full Text]
Kayagaki, N., Yamaguchi, N., Nakayama, M., Kawasaki, A., Akiba, H., Okumura, K., Yagita, H. (1999). Involvement of TNF-Related Apoptosis-Inducing Ligand in Human CD4+ T Cell-Mediated Cytotoxicity. J. Immunol. 162: 2639-2647 [Abstract] [Full Text]
Spielman, J., Lee, R. K., Podack, E. R. (1998). Perforin/Fas-Ligand Double Deficiency Is Associated with Macrophage Expansion and Severe Pancreatitis. J. Immunol. 161: 7063-7070 [Abstract] [Full Text]
Narumi, K., Kojima, A., Crystal, R. G. (1998). Adenovirus Vector-Mediated Perforin Expression Driven by a Glucocorticoid-Inducible Promoter Inhibits Tumor Growth In Vivo. Am. J. Respir. Cell Mol. Bio. 19: 936-941 [Abstract] [Full Text]
Smyth, M. J., Kelly, J. M., Baxter, A. G., Korner, H., Sedgwick, J. D. (1998). An Essential Role for Tumor Necrosis Factor in Natural Killer Cell-mediated Tumor Rejection in the Peritoneum. J. Exp. Med. 188: 1611-1619 [Abstract] [Full Text]
Sayers, T. J., Brooks, A. D., Lee, J.-K., Fenton, R. G., Komschlies, K. L., Wigginton, J. M., Winkler-Pickett, R., Wiltrout, R. H. (1998). Molecular Mechanisms of Immune-Mediated Lysis of Murine Renal Cancer: Differential Contributions of Perforin-Dependent Versus Fas-Mediated Pathways in Lysis by NK and T Cells. J. Immunol. 161: 3957-3965 [Abstract] [Full Text]
Murray, P. D., McGavern, D. B., Lin, X., Njenga, M. K., Leibowitz, J., Pease, L. R., Rodriguez, M. (1998). Perforin-Dependent Neurologic Injury in a Viral Model of Multiple Sclerosis. J. Neurosci. 18: 7306-7314 [Abstract] [Full Text]
Smyth, M. J., Krasovskis, E., Johnstone, R. W. (1998). Fas Ligand-Mediated Lysis of Self Bystander Targets by Human Papillomavirus-Specific CD8+ Cytotoxic T Lymphocytes. J. Virol. 72: 5948-5954 [Abstract] [Full Text]
Kaplan, D. H., Shankaran, V., Dighe, A. S., Stockert, E., Aguet, M., Old, L. J., Schreiber, R. D. (1998). Demonstration of an interferon gamma -dependent tumor surveillance system in immunocompetent mice. Proc. Natl. Acad. Sci. USA 95: 7556-7561 [Abstract] [Full Text]
Gasque, P., Jones, J., Singhrao, S. K., Morgan, B. (1998). Identification of an Astrocyte Cell Population from Human Brain that Expresses Perforin, a Cytotoxic Protein Implicated in Immune Defense. J. Exp. Med. 187: 451-460 [Abstract] [Full Text]
Medema, J. P., de Jong, J., Peltenburg, L. T. C., Verdegaal, E. M. E., Gorter, A., Bres, S. A., Franken, K. L. M. C., Hahne, M., Albar, J. P., Melief, C. J. M., Offringa, R. (2001). Blockade of the granzyme B/perforin pathway through overexpression of the serine protease inhibitor PI-9/SPI-6 constitutes a mechanism for immune escape by tumors. Proc. Natl. Acad. Sci. USA 98: 11515-11520 [Abstract] [Full Text]