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Tumor Stroma and the Antitumor Immune Response

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Tumor-Induced Immune Suppression

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References

  • Antonia, S. J., Mirza, N., Fricke, I., Chiappori, A., Thompson, P., Williams, N., Bepler, G., Simon, G., Janssen, W., Lee, J. H., et al. (2006). Combination of p53 cancer vaccine with chemotherapy in patients with extensive stage small cell lung cancer. Clin Cancer Res 12: 878–887.

    Article  PubMed  CAS  Google Scholar 

  • Antony, P. A., Piccirillo, C. A., Akpinarli, A., Finkelstein, S. E., Speiss, P. J., Surman, D. R., Palmer, D. C., Chan, C. C., Klebanoff, C. A., Overwijk, W. W., et al. (2005). CD8+ T cell immunity against a tumor/self-antigen is augmented by CD4+ T helper cells and hindered by naturally occurring T regulatory cells. J Immunol 174:2591–2601.

    PubMed  CAS  Google Scholar 

  • Arlen, P. M., Gulley, J. L., Parker, C., Skarupa, L., Pazdur, M., Panicali, D., Beetham, P., Tsang, K. Y., Grosenbach, D. W., Feldman, J., et al. (2006). A randomized phase II study of concurrent docetaxel plus vaccine versus vaccine alone in metastatic androgen-independent prostate cancer. Clin Cancer Res 12:1260–1269.

    Article  PubMed  CAS  Google Scholar 

  • Brent, L., and Medawar, P. (1966). Quantitative studies on tissue transplantation immunity. 8. The effects of irradiation. Proc Royal Soc Lond Ser B Biol Sci 165:413–423.

    Article  CAS  Google Scholar 

  • Bubenik, J. (2003). Tumour MHC class I downregulation and immunotherapy (review). Oncol Rep 10:2005–2008.

    PubMed  CAS  Google Scholar 

  • Casares, N., Pequignot, M. O., Tesniere, A., Ghiringhelli, F., Roux, S., Chaput, N., Schmitt, E., Hamai, A., Hervas-Stubbs, S., Obeid, M., et al. (2005). Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death. J Exp Med 202:1691–1701.

    Article  PubMed  CAS  Google Scholar 

  • Ciernik, I. F., Romero, P., Berzofsky, J. A., and Carbone, D. P. (1999). Ionizing radiation enhances immunogenicity of cells expressing a tumor-specific T-cell epitope. Int J Radiat Oncol Biol Phys 45:735–741.

    Article  PubMed  CAS  Google Scholar 

  • Demaria, S., Bhardwaj, N., McBride, W. H., and Formenti, S. C. (2005). Combining radiotherapy and immunotherapy: a revived partnership. Int J Radiat Oncol Biol Phys 63:655–666.

    Article  PubMed  Google Scholar 

  • Dudley, M. E., and Rosenberg, S. A. (2003). Adoptive-cell-transfer therapy for the treatment of patients with cancer. Nat Rev Cancer 3:666–675.

    Article  PubMed  CAS  Google Scholar 

  • Dvorak, H. F. (1986). Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 315:1650–1659.

    Article  PubMed  CAS  Google Scholar 

  • Ferrara, N., Mass, R. D., Campa, C., and Kim, R. (2007). Targeting VEGF-A to treat cancer and age-related macular degeneration. Annu Rev Med 58:491–504.

    Article  PubMed  CAS  Google Scholar 

  • Gabrilovich, D. I. (2007). Combination of chemotherapy and immunotherapy for cancer: a paradigm revisited. Lancet Oncol 8:2–3.

    Article  PubMed  Google Scholar 

  • Ganss, R., Ryschich, E., Klar, E., Arnold, B., and Hammerling, G. J. (2002). Combination of T-cell therapy and trigger of inflammation induces remodeling of the vasculature and tumor eradication. Cancer Res 62:1462–1770.

    PubMed  CAS  Google Scholar 

  • Garin-Chesa, P., Old, L. J., and Rettig, W. J. (1990). Cell surface glycoprotein of reactive stromal fibroblasts as a potential antibody target in human epithelial cancers. Proc Natl Acad Sci USA 87:7235–7239.

    Article  PubMed  CAS  Google Scholar 

  • Gattinoni, L., Finkelstein, S. E., Klebanoff, C. A., Antony, P. A., Palmer, D. C., Spiess, P. J., Hwang, L. N., Yu, Z., Wrzesinski, C., Heimann, D. M., et al. (2005a). Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells. J Exp Med 202:907–912.

    Article  CAS  Google Scholar 

  • Gattinoni, L., Klebanoff, C. A., Palmer, D. C., Wrzesinski, C., Kerstann, K., Yu, Z., Finkelstein, S. E., Theoret, M. R., Rosenberg, S. A., and Restifo, N. P. (2005b). Acquisition of full effector function in vitro paradoxically impairs the in vivo antitumor efficacy of adoptively transferred CD8+ T cells. J Clin Invest 115:1616–1626.

    Article  CAS  Google Scholar 

  • Gattinoni, L., Powell, D. J., Jr, Rosenberg, S. A., Restifo, N. P. (2006). Adoptive immunotherapy for cancer: building on success. Nat Rev Immunol 6:383–393.

    Article  PubMed  CAS  Google Scholar 

  • Gribben, J. G., Ryan, D. P., Boyajian, R., Urban, R. G., Hedley, M. L., Beach, K., Nealon, P., Matulonis, U., Campos, S., Gilligan, T. D., et al. (2005). Unexpected association between induction of immunity to the universal tumor antigen CYP1B1 and response to next therapy. Clin Cancer Res 11:4430–4436.

    Article  PubMed  CAS  Google Scholar 

  • Heath, W. R., and Carbone, F. R. (2005). Coupling and cross-presentation. Nature 434:27–28.

    Article  PubMed  CAS  Google Scholar 

  • Hicklin, D. J., Marincola, F. M., and Ferrone, S. (1999). HLA class I antigen downregulation in human cancers: T-cell immunotherapy revives an old story. Mol Med Today 5:178–186.

    Article  PubMed  CAS  Google Scholar 

  • Ho, W. Y., Blattman, J. N., Dossett, M. L., Yee, C., and Greenberg, P. D. (2003). Adoptive immunotherapy: engineering T cell responses as biologic weapons for tumor mass destruction. Cancer Cell 3:431–437.

    Article  PubMed  CAS  Google Scholar 

  • Holler, P. D., Chlewicki, L. K., and Kranz, D. M. (2003). TCRs with high affinity for foreign pMHC show self-reactivity. Nat Immunol 4:55–62.

    Article  PubMed  CAS  Google Scholar 

  • Holler, P. D., and Kranz, D. M. (2003). Quantitative analysis of the contribution of TCR/pepMHC affinity and CD8 to T cell activation. Immunity 18:255–264.

    Article  PubMed  CAS  Google Scholar 

  • Ibe, S., Qin, Z., Schuler, T., Preiss, S., and Blankenstein, T. (2001). Tumor rejection by disturbing tumor stroma cell interactions. J Exp Med 194:1549–1559.

    Article  PubMed  CAS  Google Scholar 

  • Kaminski, M. S., Zasadny, K. R., Francis, I. R., Milik, A. W., Ross, C. W., Moon, S. D., Crawford, S. M., Burgess, J. M., Petry, N. A., Butchko, G. M., et al. (1993). Radioimmunotherapy of B-cell lymphoma with [131I]anti-B1 (anti-CD20) antibody. N Engl J Med 329:459–465.

    Article  PubMed  CAS  Google Scholar 

  • Kelly, T. (2005). Fibroblast activation protein-alpha and dipeptidyl peptidase IV (CD26): cell-surface proteases that activate cell signaling and are potential targets for cancer therapy. Drug Resist Updat 8:51–58.

    Article  PubMed  CAS  Google Scholar 

  • Khong, H. T., Wang, Q. J., and Rosenberg, S. A. (2004). Identification of multiple antigens recognized by tumor-infiltrating lymphocytes from a single patient: tumor escape by antigen loss and loss of MHC expression. J Immunother 27:184–190.

    Article  PubMed  Google Scholar 

  • Kim, K. J., Li, B., Winer, J., Armanini, M., Gillett, N., Phillips, H. S., and Ferrara, N. (1993). Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 362:841–844.

    Article  PubMed  CAS  Google Scholar 

  • Klebanoff, C. A., Gattinoni, L., Torabi-Parizi, P., Kerstann, K., Cardones, A. R., Finkelstein, S. E., Palmer, D. C., Antony, P. A., Hwang, S. T., Rosenberg, S. A., et al. (2005). Central memory self/tumor-reactive CD8+ T cells confer superior antitumor immunity compared with effector memory T cells. Proc Natl Acad Sci USA 102:9571–9576.

    Article  PubMed  CAS  Google Scholar 

  • Klein, E., and Klein, G. (1972). Specificity of homograft rejection in vivo, assessed by inoculation of artificially mixed compatible and incompatible tumor cells. Cell Immunol 5:201–208.

    Article  Google Scholar 

  • Lake, R. A., and Robinson, B. W. (2005). Immunotherapy and chemotherapy—a practical partnership. Nat Rev Cancer 5:397–405.

    Article  PubMed  CAS  Google Scholar 

  • Liu, K., Caldwell, S. A., and Abrams, S. I. (2005). Immune selection and emergence of aggressive tumor variants as negative consequences of Fas-mediated cytotoxicity and altered IFN-gamma-regulated gene expression. Cancer Res 65:4376–4388.

    Article  PubMed  CAS  Google Scholar 

  • Lugade, A. A., Moran, J. P., Gerber, S. A., Rose, R. C., Frelinger, J. G., and Lord, E. M. (2005). Local radiation therapy of B16 melanoma tumors increases the generation of tumor antigen-specific effector cells that traffic to the tumor. J Immunol 174:7516–7523.

    PubMed  CAS  Google Scholar 

  • Lynch, T. J., Bell, D. W., Sordella, R., Gurubhagavatula, S., Okimoto, R. A., Brannigan, B. W., Harris, P. L., Haserlat, S. M., Supko, J. G., Haluska, F. G., et al. (2004). Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350:2129–2139.

    Article  PubMed  CAS  Google Scholar 

  • Morgan, R. A., Dudley, M. E., Wunderlich, J. R., Hughes, M. S., Yang, J. C., Sherry, R. M., Royal, R. E., Topalian, S. L., Kammula, U. S., Restifo, N. P., et al. (2006). Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 314:126–129.

    Article  PubMed  CAS  Google Scholar 

  • Nair, S., Boczkowski, D., Moeller, B., Dewhirst, M., Vieweg, J., and Gilboa, E. (2003). Synergy between tumor immunotherapy and antiangiogenic therapy. Blood 102:964–971.

    Article  PubMed  CAS  Google Scholar 

  • Neijssen, J., Herberts, C., Drijfhout, J. W., Reits, E., Janssen, L., and Neefjes, J. (2005). Cross-presentation by intercellular peptide transfer through gap junctions. Nature 434:83–88.

    Article  PubMed  CAS  Google Scholar 

  • Niederman, T. M., Ghogawala, Z., Carter, B. S., Tompkins, H. S., Russell, M. M., and Mulligan, R. C. (2002). Antitumor activity of cytotoxic T lymphocytes engineered to target vascular endothelial growth factor receptors. Proc Natl Acad Sci USA 99:7009–7014.

    Article  PubMed  CAS  Google Scholar 

  • Nowak, A. K., Lake, R. A., Marzo, A. L., Scott, B., Heath, W. R., Collins, E. J., Frelinger, J. A., and Robinson, B. W. (2003). Induction of tumor cell apoptosis in vivo increases tumor antigen cross-presentation, cross-priming rather than cross-tolerizing host tumor-specific CD8 T cells. J Immunol 170:4905–4913.

    PubMed  CAS  Google Scholar 

  • Prehn, R. T. (1973). Destruction of tumor as an “innocent bystander” in an immune response specifically directed against nontumor antigens. Isr J Med Sci 9:375–379.

    PubMed  CAS  Google Scholar 

  • Reits, E. A., Hodge, J. W., Herberts, C. A., Groothuis, T. A., Chakraborty, M., Wansley, E. K., Camphausen, K., Luiten, R. M., de Ru, A. H., Neijssen, J., et al. (2006). Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy. J Exp Med 203:1259–1271.

    Article  PubMed  CAS  Google Scholar 

  • Sanchez-Perez, L., Kottke, T., Diaz, R. M., Ahmed, A., Thompson, J., Chong, H., Melcher, A., Holmen, S., Daniels, G., and Vile, R. G. (2005). Potent selection of antigen loss variants of B16 melanoma following inflammatory killing of melanocytes in vivo. Cancer Res 65:2009–2017.

    Article  PubMed  CAS  Google Scholar 

  • Schreiber, H. (ed.) (2003). Tumor Immunology, 5th edn. Philadelphia, PA: Lippincott-Williams & Wilkins, pp. 1557–1592.

    Google Scholar 

  • Scott, A. M., Wiseman, G., Welt, S., Adjei, A., Lee, F. T., Hopkins, W., Divgi, C. R., Hanson, L. H., Mitchell, P., Gansen, D. N., et al. (2003). A phase I dose-escalation study of sibrotuzumab in patients with advanced or metastatic fibroblast activation protein-positive cancer. Clin Cancer Res 9:1639–1647.

    PubMed  CAS  Google Scholar 

  • Seemayer, T. A., Lagace, R., Schurch, W., and Tremblay, G. (1979). Myofibroblasts in the stroma of invasive and metastatic carcinoma: a possible host response to neoplasia. Am J Surg Pathol 3:525–533.

    Article  PubMed  CAS  Google Scholar 

  • Slamon, D. J., Leyland-Jones, B., Shak, S., Fuchs, H., Paton, V., Bajamonde, A., Fleming, T., Eiermann, W., Wolter, J., Pegram, M., et al. (2001). Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344:783–792.

    Article  PubMed  CAS  Google Scholar 

  • Spiotto, M. T., Rowley, D. A., and Schreiber, H. (2004). Bystander elimination of antigen loss variants in established tumors. Nat Med 10:294–298.

    Article  PubMed  CAS  Google Scholar 

  • Spiotto, M. T., and Schreiber, H. (2005). Rapid destruction of the tumor microenvironment by CTLs recognizing cancer-specific antigens cross-presented by stromal cells. Cancer Immun 5:8.

    PubMed  Google Scholar 

  • Sweeney, C. J., Miller, K. D., and Sledge, G. W., Jr (2003). Resistance in the anti-angiogenic era: nay-saying or a word of caution? Trends Mol Med 9:24–29.

    Article  PubMed  CAS  Google Scholar 

  • Weissman, I. L. (1973). Tumor immunity in vivo: evidence that immune destruction of tumor leaves “bystander” cells intact. J Natl Cancer Inst 51:443–448.

    PubMed  CAS  Google Scholar 

  • Wesley, U. V., Albino, A. P., Tiwari, S., and Houghton, A. N. (1999). A role for dipeptidyl peptidase IV in suppressing the malignant phenotype of melanocytic cells. J Exp Med 190:311–322.

    Article  PubMed  CAS  Google Scholar 

  • Wheeler, C. J., Das, A., Liu, G., Yu, J. S., and Black, K. L. (2004). Clinical responsiveness of glioblastoma multiforme to chemotherapy after vaccination. Clin Cancer Res 10:5316–5326.

    Article  PubMed  CAS  Google Scholar 

  • Yamshchikov, G. V., Mullins, D. W., Chang, C. C., Ogino, T., Thompson, L., Presley, J., Galavotti, H., Aquila, W., Deacon, D., Ross, W., et al. (2005). Sequential immune escape and shifting of T cell responses in a long-term survivor of melanoma. J Immunol 174:6863–6871.

    PubMed  CAS  Google Scholar 

  • Yang, J. C., Haworth, L., Sherry, R. M., Hwu, P., Schwartzentruber, D. J., Topalian, S. L., Steinberg, S. M., Chen, H. X., and Rosenberg, S. A. (2003). A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 349:427–434.

    Article  PubMed  CAS  Google Scholar 

  • Yu, Z., Theoret, M. R., Touloukian, C. E., Surman, D. R., Garman, S. C., Feigenbaum, L., Baxter, T. K., Baker, B. M., and Restifo, N. P. (2004). Poor immunogenicity of a self/tumor antigen derives from peptide-MHC-I instability and is independent of tolerance. J Clin Invest 114:551–559.

    Article  PubMed  CAS  Google Scholar 

  • Zhang, B., Bowerman, N. A., Salama, J. K., Schmidt, H., Spiotto, M. T., Schietinger, A., Yu, P., Fu, Y. X., Weichselbaum, R. R., Rowley, D. A., et al. (2007). Induced sensitization of tumor stroma leads to eradication of established cancer by T cells. J Exp Med 204:49–55.

    Article  PubMed  CAS  Google Scholar 

  • Zhou, G., Lu, Z., McCadden, J. D., Levitsky, H. I., and Marson, A. L. (2004). Reciprocal changes in tumor antigenicity and antigen-specific T cell function during tumor progression. J Exp Med 200:1581–1592.

    Article  PubMed  CAS  Google Scholar 

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Zhang, B., Rowley, D.A., Schreiber, H. (2008). Tumor Stroma and the Antitumor Immune Response. In: Gabrilovich, D.I., Hurwitz, A.A. (eds) Tumor-Induced Immune Suppression. Springer, New York, NY. https://doi.org/10.1007/978-0-387-69118-3_13

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