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Signaling Pathways in Antigen-Presenting Cells Involved in the Induction of Antigen-Specific T-Cell Tolerance

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Tumor-Induced Immune Suppression

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References

  • Adler, A. J., Marsh, D. W., Yochum, G. S., Guzzo, J. L., Nigam, A., Nelson, W. G. and Pardoll, D. M. (1998). CD4(+) T cell tolerance to parenchymal self-antigens requires presentation by bone marrow-derived antigen-presenting cells [In Process Citation]. J Exp Med 187(10):1555–1564.

    Article  PubMed  CAS  Google Scholar 

  • Alexander, W. S., Starr, R., Fenner, J. E., Scott, C. L., Handman, E., Sprigg, N. S., Corbin, J. E., Cornish, A. L., Darwiche, R., Owczarek, C. M., Kay, T. W., Nicola, N. A., Hertzog, P. J., Metcalf, D. and Hilton, D. J. (1999). SOCS1 is a critical inhibitor of interferon gamma signaling and prevents the potentially fatal neonatal actions of this cytokine. Cell 98(5): 597–608.

    Article  PubMed  CAS  Google Scholar 

  • Belz, G. T., Behrens, G. M., Smith, C. M., Miller, J. F., Jones, C., Lejon, K., Fathman, C. G., Mueller, S. N., Shortman, K., Carbone, F. R. and Heath, W. R. (2002). The CD8alpha(+) dendritic cell is responsible for inducing peripheral self-tolerance to tissue-associated antigens. J Exp Med 196(8):1099–1104.

    Article  PubMed  CAS  Google Scholar 

  • Benkhart, E. M., Siedlar, M., Wedel, A., Werner, T. and Ziegler-Heitbrock, H. W. (2000). Role of Stat3 in lipopolysaccharide-induced IL-10 gene expression. J Immunol 165(3):1612–1617.

    PubMed  CAS  Google Scholar 

  • Bogen, B. (1996). Peripheral T cell tolerance as a tumor escape mechanism: deletion of CD4+ T cells specific for a monoclonal immunoglobulin idiotype secreted by a plasmacytoma. Eur J Immunol 26(11):2671–2679.

    Article  PubMed  CAS  Google Scholar 

  • Bonifaz, L., Bonnyay, D., Mahnke, K., Rivera, M., Nussenzweig, M. C. and Steinman, R. M. (2002). Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance. J Exp Med 196(12):1627–1638.

    Article  PubMed  CAS  Google Scholar 

  • Boon, T. and van der Bruggen, P. (1996). Human tumor antigens recognized by T lymphocytes. J Exp Med 183(3):725–729.

    Article  PubMed  CAS  Google Scholar 

  • Borg, C., Terme, M., Taieb, J., Menard, C., Flament, C., Robert, C., Maruyama, K., Wakasugi, H., Angevin, E., Thielemans, K., Le Cesne, A., Chung-Scott, V., Lazar, V., Tchou, I., Crepineau, F., Lemoine, F., Bernard, J., Fletcher, J. A., Turhan, A., Blay, J. Y., Spatz, A., Emile, J. F., Heinrich, M. C., Mecheri, S., Tursz, T. and Zitvogel, L. (2004). Novel mode of action of c-kit tyrosine kinase inhibitors leading to NK cell-dependent antitumor effects. J Clin Invest 114(3): 379–388.

    Article  PubMed  CAS  Google Scholar 

  • Bromberg, J. and Darnell, J. E., Jr (2000). The role of STATs in transcriptional control and their impact on cellular function. Oncogene 19(21):2468–2473.

    Article  PubMed  CAS  Google Scholar 

  • Camenisch, T. D., Koller, B. H., Earp, H. S. and Matsushima, G. K. (1999). A novel receptor tyrosine kinase, Mer, inhibits TNF-alpha production and lipopolysaccharide-induced endotoxic shock. J Immunol 162:3498–3503.

    PubMed  CAS  Google Scholar 

  • Casiano, C. A. and Tan, E. M. (1996). Recent developments in the understanding of antinuclear autoantibodies. Int Arch Allergy Immunol 111(4):308–313.

    Article  PubMed  CAS  Google Scholar 

  • Chan, C. W., Crafton, E., Fan, H. N., Flook, J., Yoshimura, K., Skarica, M., Brockstedt, D., Dubensky, T. W., Stins, M. F., Lanier, L. L., Pardoll, D. M. and Housseau, F. (2006). Interferon-producing killer dendritic cells provide a link between innate and adaptive immunity. Nat Med 12(2):207–213.

    Article  PubMed  CAS  Google Scholar 

  • Cheng, F., Wang, H. W., Cuenca, A., Huang, M., Ghansah, T., Brayer, J., Kerr, W. G., Takeda, K., Akira, S., Schoenberger, S. P., Yu, H., Jove, R. and Sotomayor, E. M. (2003). A critical role for Stat3 signaling in immune tolerance. Immunity 19(3):425–436.

    Article  PubMed  CAS  Google Scholar 

  • Chong, M. M., Cornish, A. L., Darwiche, R., Stanley, E. G., Purton, J. F., Godfrey, D. I., Hilton, D. J., Starr, R., Alexander, W. S. and Kay, T. W. (2003). Suppressor of cytokine signaling-1 is a critical regulator of interleukin-7-dependent CD8+ T cell differentiation. Immunity 18(4):475–487.

    Article  PubMed  CAS  Google Scholar 

  • Cohen, P. L., Caricchio, R., Abraham, V., Camenisch, T. D., Jennette, J. C., Roubey, R. A. S., Earp, H. S., Matsushima, G. and Reap, E. A. (2002). Delayed apoptotic cell clearance and lupus-like autoimmunity in mice lacking the c-mer membrane tyrosine kinase. J Exp Med 196:135–140.

    Article  PubMed  CAS  Google Scholar 

  • Correll, P. H., Morrison, A. C. and Lutz, M. A. (2004). Receptor tyrosine kinases and the regulation of macrophage activation. J Leukoc Biol 75:731–737.

    Article  PubMed  CAS  Google Scholar 

  • Cuenca, A., Cheng, F., Wang, H., Brayer, J., Horna, P., Gu, L., Bien, H., Borrello, I. M., Levitsky, H. I. and Sotomayor, E. M. (2003). Extra-lymphatic solid tumor growth is not immunologically ignored and results in early induction of antigen-specific T-cell anergy: dominant role of cross-tolerance to tumor antigens. Cancer Res 63(24):9007–9015.

    PubMed  CAS  Google Scholar 

  • Darnell, J. E., Jr (1997). STATs and gene regulation. Science 277(5332):1630–1635.

    Article  PubMed  CAS  Google Scholar 

  • de Jonge, W. J., van der Zanden, E. P., The, F. O., Bijlsma, M. F., van Westerloo, D. J., Bennink, R. J., Berthoud, H. R., Uematsu, S., Akira, S., van den Wijngaard, R. M. and Boeckxstaens, G. E. (2005). Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway. Nat Immunol 6(8):844–851.

    Article  PubMed  CAS  Google Scholar 

  • Druker, B. J., Tamura, S., Buchdunger, E., Ohno, S., Segal, G. M., Fanning, S., Zimmermann, J. and Lydon, N. B. (1996). Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med 2(5):561–566.

    Article  PubMed  CAS  Google Scholar 

  • El Kasmi, K. C., Holst, J., Coffre, M., Mielke, L., de Pauw, A., Lhocine, N., Smith, A. M., Rutschman, R., Kaushal, D., Shen, Y., Suda, T., Donnelly, R. P., Myers, M. G., Jr, Alexander, W., Vignali, D. A., Watowich, S. S., Ernst, M., Hilton, D. J. and Murray, P. J. (2006). General nature of the STAT3-activated anti-inflammatory response. J Immunol 177(11):7880–7888.

    PubMed  CAS  Google Scholar 

  • Endo, T. A., Masuhara, M., Yokouchi, M., Suzuki, R., Sakamoto, H., Mitsui, K., Matsumoto, A., Tanimura, S., Ohtsubo, M., Misawa, H., Miyazaki, T., Leonor, N., Taniguchi, T., Fujita, T., Kanakura, Y., Komiya, S. and Yoshimura, A. (1997). A new protein containing an SH2 domain that inhibits JAK kinases. Nature 387:921–924.

    Article  PubMed  CAS  Google Scholar 

  • Evel-Kabler, K., Song, X. T., Aldrich, M., Huang, X. F. and Chen, S. Y. (2006). SOCS1 restricts dendritic cells’ ability to break self tolerance and induce antitumor immunity by regulating IL-12 production and signaling. J Clin Invest 116(1):90–100.

    Article  PubMed  CAS  Google Scholar 

  • Fadok, V. A., Bratton, D. L., Konowal, A., Freed, P. W., Westcott, J. Y. and Henson, P. M. (1998). Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. J Clin Invest 101(4):890–898.

    Article  PubMed  CAS  Google Scholar 

  • Fuchs, E. J. and Matzinger, P. (1992). B cells turn off virgin but not memory T cells. Science 258(5085):1156–1159.

    Article  PubMed  CAS  Google Scholar 

  • Ghosh, S., May, M. J. and Kopp, E. B. (1998). NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol 16:225–260.

    Article  PubMed  CAS  Google Scholar 

  • Guermonprez, P., Valladeau, J., Zitvogel, L., Thery, C. and Amigorena, S. (2002). Antigen presentation and T cell stimulation by dendritic cells. Annu Rev Immunol 20:621–667.

    Article  PubMed  CAS  Google Scholar 

  • Hanada, T., Yoshida, H., Kato, S., Tanaka, K., Masutani, K., Tsukada, J., Nomura, Y., Mimata, H., Kubo, M. and Yoshimura, A. (2003). Suppressor of cytokine signaling-1 is essential for suppressing dendritic cell activation and systemic autoimmunity. Immunity 19:437–450.

    Article  PubMed  CAS  Google Scholar 

  • Hawiger, D., Inaba, K., Dorsett, Y., Guo, M., Mahnke, K., Rivera, M., Ravetch, J. V., Steinman, R. M. and Nussenzweig, M. C. (2001). Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J Exp Med 194(6):769–779.

    Article  PubMed  CAS  Google Scholar 

  • Heath, W. R., Belz, G. T., Behrens, G. M., Smith, C. M., Forehan, S. P., Parish, I. A., Davey, G. M., Wilson, N. S., Carbone, F. R. and Villadangos, J. A. (2004). Cross-presentation, dendritic cell subsets, and the generation of immunity to cellular antigens. Immunol Rev 199:9–26.

    Article  PubMed  CAS  Google Scholar 

  • Heinrich, M. C., Blanke, C. D., Druker, B. J. and Corless, C. L. (2002). Inhibition of KIT tyrosine kinase activity: a novel molecular approach to the treatment of KIT-positive malignancies. J Clin Oncol 20(6):1692–1703.

    Article  PubMed  CAS  Google Scholar 

  • Heinrich, M. C., Corless, C. L., Demetri, G. D., Blanke, C. D., von Mehren, M., Joensuu, H., McGreevey, L. S., Chen, C. J., Van den Abbeele, A. D., Druker, B. J., Kiese, B., Eisenberg, B., Roberts, P. J., Singer, S., Fletcher, C. D., Silberman, S., Dimitrijevic, S. and Fletcher, J. A. (2003). Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 21(23):4342–4349.

    Article  PubMed  CAS  Google Scholar 

  • Hida, S., Ogasawara, K., Sato, K., Abe, M., Takayanagi, H., Yokochi, T., Sato, T., Hirose, S., Shirai, T., Taki, S. and Taniguchi, T. (2000). CD8(+) T cell-mediated skin disease in mice lacking IRF-2, the transcriptional attenuator of interferon-alpha/beta signaling [In Process Citation]. Immunity 13(5):643–655.

    Article  PubMed  CAS  Google Scholar 

  • Hoentjen, F., Sartor, R. B., Ozaki, M. and Jobin, C. (2005). STAT3 regulates NF-kappaB recruitment to the IL-12p40 promoter in dendritic cells. Blood 105:689–696.

    Article  PubMed  CAS  Google Scholar 

  • Horna, P. and Sotomayor, E. M. (2007). Cellular and molecular mechanisms of tumor-induced T-cell tolerance. Curr Cancer Drug Targets 7(1):41–53.

    Article  PubMed  CAS  Google Scholar 

  • Huang, F. P., Platt, N., Wykes, M., Major, J. R., Powell, T. J., Jenkins, C. D. and MacPherson, G. G. (2000). A discrete subpopulation of dendritic cells transports apoptotic intestinal epithelial cells to T cell areas of mesenteric lymph nodes [see comments]. J Exp Med 191(3): 435–444.

    Article  PubMed  CAS  Google Scholar 

  • Itano, A. A. and Jenkins, M. K. (2003). Antigen presentation to naive CD4 T cells in the lymph node. Nat Immunol 4(8):733–739.

    Article  PubMed  CAS  Google Scholar 

  • Kantarjian, H., Sawyers, C., Hochhaus, A., Guilhot, F., Schiffer, C., Gambacorti-Passerini, C., Niederwieser, D., Resta, D., Capdeville, R., Zoellner, U., Talpaz, M., Druker, B., Goldman, J., O’Brien, S. G., Russell, N., Fischer, T., Ottmann, O., Cony-Makhoul, P., Facon, T., Stone, R., Miller, C., Tallman, M., Brown, R., Schuster, M., Loughran, T., Gratwohl, A., Mandelli, F., Saglio, G., Lazzarino, M., Russo, D., Baccarani, M. and Morra, E. (2002). Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med 346(9):645–652.

    Article  PubMed  CAS  Google Scholar 

  • Kobayashi, M., Kweon, M.-N., Kuwata, H., Schreiber, R., Kiyono, H., Takeda, K. and Akira, S. (2003). Toll-like receptor-dependent production of IL-12p40 causes chronic enterocolitis in myeloid cell-specific Stat3-deficient mice. J Clin Invest 111:1297–1308.

    Article  PubMed  CAS  Google Scholar 

  • Kotenko, S. V. and Pestka, S. (2000). Jak-Stat signal transduction pathway through the eyes of cytokine class II receptor complexes. Oncogene 19(21):2557–2565.

    Article  PubMed  CAS  Google Scholar 

  • Kurts, C., Carbone, F. R., Barnden, M., Blanas, E., Allison, J., Heath, W. R. and Miller, J. F. (1997). CD4+ T cell help impairs CD8+ T cell deletion induced by cross- presentation of self-antigens and favors autoimmunity. J Exp Med 186(12):2057–2062.

    Article  PubMed  CAS  Google Scholar 

  • Lai, C. and Lemke, G. (1991). An extended family of protein-tyrosine kinase genes differentially expressed in the vertebrate nervous system. Neuron 6(5):691–704.

    Article  PubMed  CAS  Google Scholar 

  • Lang, R., Patel, D., Morris, J., Rutschman, R. and Murray, P. (2002). Shaping gene expression in activated and resting primary macrophages by IL-10. J Immunol 169:2253–2263.

    PubMed  CAS  Google Scholar 

  • Lang, R., Pauleau, A. L., Parganas, E., Takahashi, Y., Mages, J., Ihle, J. N., Rutschman, R. and Murray, P. J. (2003). SOCS3 regulates the plasticity of gp130 signaling. Nat Immunol 4(6): 546–550.

    Article  PubMed  CAS  Google Scholar 

  • Lassila, O., Vainio, O. and Matzinger, P. (1988). Can B cells turn on virgin T cells? Nature 334(6179):253–255.

    Article  PubMed  CAS  Google Scholar 

  • Lee, P. P., Yee, C., Savage, P. A., Fong, L., Brockstedt, D., Weber, J. S., Johnson, D., Swetter, S., Thompson, J., Greenberg, P. D., Roederer, M. and Davis, M. M. (1999). Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients. Nat Med 5(6):677–685.

    Article  PubMed  CAS  Google Scholar 

  • Lemke, G. and Lu, Q. (2003). Macrophage regulation by Tyro 3 family receptors. Curr Opin Immunol 15:31–36.

    Article  PubMed  CAS  Google Scholar 

  • Lu, Q. and Lemke, G. (2001). Homeostatic regulation of the immune system by receptor tyrosine kinases of the Tyro 3 family. Science 293(5528):306–311.

    Article  PubMed  CAS  Google Scholar 

  • Marine, J. C., Topham, D. J., McKay, C., Wang, D., Parganas, E., Stravopodis, D., Yoshimura, A. and Ihle, J. N. (1999). SOCS1 deficiency causes a lymphocyte-dependent perinatal lethality. Cell 98:609–616.

    Article  PubMed  CAS  Google Scholar 

  • Mevorach, D., Zhou, J. L., Song, X. and Elkon, K. B. (1998). Systemic exposure to irradiated apoptotic cells induces autoantibody production. J Exp Med 188(2):387–392.

    Article  PubMed  CAS  Google Scholar 

  • Miyazaki, T., Suzuki, G. and Yamamura, K. (1993). The role of macrophages in antigen presentation and T cell tolerance. Int Immunol 5(9):1023–1033.

    Article  PubMed  CAS  Google Scholar 

  • Morgan, D. J., Kreuwel, H. T., Fleck, S., Levitsky, H. I., Pardoll, D. M. and Sherman, L. A. (1998). Activation of low avidity CTL specific for a self epitope results in tumor rejection but not autoimmunity. J Immunol 160(2):643–651.

    PubMed  CAS  Google Scholar 

  • Munn, D., Sharma, M., Hou, D., Baban, B., Lee, J., Antonia, S., Messina, J., Chandler, P., Koni, P. and Mellor, A. (2004). Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in tumor-draining lymph nodes. J Clin Invest 114:280–290.

    Article  PubMed  CAS  Google Scholar 

  • Munn, D., Sharma, M., Lee, J., Jhaver, K., Johnson, T., Keskin, D., Marshall, B., Chandler, P., Antonia, S., Burgess, R., Slingluff, J. C. and Mellor, A. (2002). Potential regulatory function of human dendritic cells expressing indoleamine 2,3-dioxygenase. Science 297:1867–1870.

    Article  PubMed  CAS  Google Scholar 

  • Murray, P. (2005). The primary mechanism of the IL-10-regulated antiinflammatory response is to selectively inhibit transcription. Proc Natl Acad Sci USA 102:8686–8691.

    Article  PubMed  CAS  Google Scholar 

  • Nefedova, Y., Cheng, P., Gilkes, D., Blaskovich, M., Beg, A. A., Sebti, S. M. and Gabrilovich, D. I. (2005). Activation of dendritic cells via inhibition of Jak2/STAT3 signaling. J Immunol 175(7):4338–4346.

    PubMed  CAS  Google Scholar 

  • Noonan, K., Matsui, W., Serafini, P., Carbley, R., Tan, G., Khalili, J., Bonyhadi, M., Levitsky, H., Whartenby, K. and Borrello, I. (2005). Activated marrow-infiltrating lymphocytes effectively target plasma cells and their clonogenic precursors. Cancer Res 65(5):2026–2034.

    Article  PubMed  CAS  Google Scholar 

  • Ohlen, C., Kalos, M., Hong, D. J., Shur, A. C. and Greenberg, P. D. (2001). Expression of a tolerizing tumor antigen in peripheral tissue does not preclude recovery of high-affinity CD8+ T cells or CTL immunotherapy of tumors expressing the antigen. J Immunol 166(4):2863–2870.

    PubMed  CAS  Google Scholar 

  • Overwijk, W. W., Theoret, M. R., Finkelstein, S. E., Surman, D. R., de Jong, L. A., Vyth-Dreese, F. A., Dellemijn, T. A., Antony, P. A., Spiess, P. J., Palmer, D. C., Heimann, D. M., Klebanoff, C. A., Yu, Z., Hwang, L. N., Feigenbaum, L., Kruisbeek, A. M., Rosenberg, S. A. and Restifo, N. P. (2003). Tumor regression and autoimmunity after reversal of a functionally tolerant state of self-reactive CD8+ T cells. J Exp Med 198(4):569–580.

    Article  PubMed  CAS  Google Scholar 

  • Pardoll, D. (2003). Does the immune system see tumors as foreign or self? Annu Rev Immunol 21:807–839.

    Article  PubMed  CAS  Google Scholar 

  • Qin, H., Wilson, C., Roberts, K., Baker, B., Zhao, X. and Benveniste, E. (2006). IL-10 inhibits lipopolysaccharide-induced CD40 gene expression through induction of suppressor of cytokine signaling-3. J Immunol 177:7761–7771.

    PubMed  CAS  Google Scholar 

  • Ramana, C. V., Chatterjee-Kishore, M., Nguyen, H. and Stark, G. R. (2000). Complex roles of Stat1 in regulating gene expression. Oncogene 19(21):2619–2627.

    Article  PubMed  CAS  Google Scholar 

  • Ravetch, J. V. and Lanier, L. L. (2000). Immune inhibitory receptors [In Process Citation]. Science 290(5489):84–89.

    Article  PubMed  CAS  Google Scholar 

  • Ronchese, F. and Hausmann, B. (1993). B lymphocytes in vivo fail to prime naive T cells but can stimulate antigen-experienced T lymphocytes. J Exp Med 177(3):679–690.

    Article  PubMed  CAS  Google Scholar 

  • Ronchetti, A., Rovere, P., Iezzi, G., Galati, G., Heltai, S., Protti, M. P., Garancini, M. P., Manfredi, A. A., Rugarli, C. and Bellone, M. (1999). Immunogenicity of apoptotic cells in vivo: role of antigen load, antigen-presenting cells, and cytokines. J Immunol 163(1):130–136.

    PubMed  CAS  Google Scholar 

  • Rosen, A. and Casciola-Rosen, L. (1999). Autoantigens as substrates for apoptotic proteases: implications for the pathogenesis of systemic autoimmune disease. Cell Death Differ 6(1): 6–12.

    Article  PubMed  CAS  Google Scholar 

  • Rosenberg, S. A. (1995). The development of new cancer therapies based on the molecular identification of cancer regression antigens. Cancer J Sci Am 1(2):90.

    Google Scholar 

  • Scheinecker, C., McHugh, R., Shevach, E. M. and Germain, R. N. (2002). Constitutive presentation of a natural tissue autoantigen exclusively by dendritic cells in the draining lymph node. J Exp Med 196(8):1079–1090.

    Article  PubMed  CAS  Google Scholar 

  • Scott, R. S., McMahon, E. J., Pop, S. M., Reap, E. A., Caricchio, R., Cohen, P. L., Earp, H. S. and Matsushima, G. K. (2001). Phagocytosis and clearance of apoptotic cells is mediated by MER. Nature 411(6834):207–211.

    Article  PubMed  CAS  Google Scholar 

  • Sen, P., Wallet, M., Yi, Z., Huang, Y., Henderson, M., Mathews, C., Earp, H., Matsushima, G., Baldwin, J. A. and Tisch, R. (2007). Apoptotic cells induce Mer tyrosine kinase-dependent blockade of NF-kappaB activation in dendritic cells. Blood 109:653–660.

    Article  PubMed  CAS  Google Scholar 

  • Shrikant, P. and Mescher, M. F. (1999). Control of syngeneic tumor growth by activation of CD8+ T cells: efficacy is limited by migration away from the site and induction of nonresponsiveness. J Immunol 162(5):2858–2866.

    PubMed  CAS  Google Scholar 

  • Soltys, J., Bonfield, T., Chmiel, J. and Berger, M. (2002). Functional IL-10 deficiency in the lung of cystic fibrosis (cftr(-/-)) and IL-10 knockout mice causes increased expression and function of B7 costimulatory molecules on alveolar macrophages. J Immunol 168(4):1903–1910.

    PubMed  CAS  Google Scholar 

  • Sotomayor, E. M., Borrello, I. and Levitsky, H. I. (1996). Tolerance and cancer: a critical issue in tumor immunology. Crit Rev Oncog 7(5–6):433–456.

    PubMed  CAS  Google Scholar 

  • Sotomayor, E. M., Borrello, I., Rattis, F. M., Cuenca, A. G., Abrams, J., Staveley-O’Carroll, K. and Levitsky, H. I. (2001). Cross-presentation of tumor antigens by bone marrow-derived antigen-presenting cells is the dominant mechanism in the induction of T-cell tolerance during B-cell lymphoma progression. Blood 98(4):1070–1077.

    Article  PubMed  CAS  Google Scholar 

  • Staveley-O’Carroll, K., Sotomayor, E., Montgomery, J., Borrello, I., Hwang, L., Fein, S., Pardoll, D. and Levitsky, H. (1998). Induction of antigen-specific T cell anergy: an early event in the course of tumor progression. Proc Natl Acad Sci USA 95(3):1178–1183.

    Article  PubMed  CAS  Google Scholar 

  • Steinman, R. M., Hawiger, D. and Nussenzweig, M. C. (2003). Tolerogenic dendritic cells. Annu Rev Immunol 21:685–711.

    Article  PubMed  CAS  Google Scholar 

  • Stitt, T. N., Conn, G., Gore, M., Lai, C., Bruno, J., Radziejewski, C., Mattsson, K., Fisher, J., Gies, D. R., Jones, P. F. et al. (1995). The anticoagulation factor protein S and its relative, Gas6, are ligands for the Tyro 3/Axl family of receptor tyrosine kinases. Cell 80(4):661–670.

    Article  PubMed  CAS  Google Scholar 

  • Taieb, J., Chaput, N., Menard, C., Apetoh, L., Ullrich, E., Bonmort, M., Pequignot, M., Casares, N., Terme, M., Flament, C., Opolon, P., Lecluse, Y., Metivier, D., Tomasello, E., Vivier, E., Ghiringhelli, F., Martin, F., Klatzmann, D., Poynard, T., Tursz, T., Raposo, G., Yagita, H., Ryffel, B., Kroemer, G. and Zitvogel, L. (2006). A novel dendritic cell subset involved in tumor immunosurveillance. Nat Med 12(2):214–219.

    Article  PubMed  CAS  Google Scholar 

  • Takeda, K., Clausen, B. E., Kaisho, T., Tsujimura, T., Terada, N., Forster, I. and Akira, S. (1999). Enhanced Th1 activity and development of chronic enterocolitis in mice devoid of Stat3 in macrophages and neutrophils. Immunity 10:39–49.

    Article  PubMed  CAS  Google Scholar 

  • Taylor, P. R., Carugati, A., Fadok, V. A., Cook, H. T., Andrews, M., Carroll, M. C., Savill, J. S., Henson, P. M., Botto, M. and Walport, M. J. (2000). A hierarchical role for classical pathway complement proteins in the clearance of apoptotic cells in vivo. J Exp Med 192(3):359–366.

    Article  PubMed  CAS  Google Scholar 

  • Tivol, E. A., Borriello, F., Schweitzer, A. N., Lynch, W. P., Bluestone, J. A. and Sharpe, A. H. (1995). Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity 3(5):541–547.

    Article  PubMed  CAS  Google Scholar 

  • Trinchieri, G. (2003). Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol 3:133–146.

    Article  PubMed  CAS  Google Scholar 

  • Voll, R. E., Herrmann, M., Roth, E. A., Stach, C., Kalden, J. R. and Girkontaite, I. (1997). Immunosuppressive effects of apoptotic cells [letter]. Nature 390(6658):350–351.

    Article  PubMed  CAS  Google Scholar 

  • Wang, H., Cheng, F., Cuenca, A., Horna, P., Zheng, Z., Bhalla, K. and Sotomayor, E. M. (2004a). Imatinib mesylate (STI-571) enhances antigen presenting cell function and overcomes tumor-induced CD4+ T-cell tolerance. Blood 105(3):1135–43.

    Article  CAS  Google Scholar 

  • Wang, H., Liao, H., Ochani, M., Justiniani, M., Lin, X., Yang, L., Al-Abed, Y., Wang, H., Metz, C., Miller, E. J., Tracey, K. J. and Ulloa, L. (2004b). Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nat Med 10(11):1216–1221.

    Article  CAS  Google Scholar 

  • Watson, G. A. and Lopez, D. M. (1995). Aberrant antigen presentation by macrophages from tumor-bearing mice is involved in the down-regulation of their T cell responses. J Immunol 155(6):3124–3134.

    PubMed  CAS  Google Scholar 

  • Welte, T., Zhang, S. S., Wang, T., Zhang, Z., Hesslein, D. G., Yin, Z., Kano, A., Iwamoto, Y., Li, E., Craft, J. E., Bothwell, A. L., Fikrig, E., Koni, P. A., Flavell, R. A. and Fu, X. Y. (2003). STAT3 deletion during hematopoiesis causes Crohn’s disease-like pathogenesis and lethality: a critical role of STAT3 in innate immunity. Proc Natl Acad Sci USA 100(4):1879–1884.

    Article  PubMed  CAS  Google Scholar 

  • Williams, L., Bradley, L., Smith, A. and Foxwell, B. (2004). Signal transducer and activator of Transcription 3 is the dominant mediator of the anti-inflammatory effects of IL-10 in human macrophages. J Immunol 172:567–576.

    PubMed  CAS  Google Scholar 

  • Williams, L., Sarma, U., Willets, K., Smallie, T. and Brennan, F. (2007). Expression of constitutively active STAT3 can replicate the cytokine-suppressive activity of interleukin-10 in human primary macrophages. J Biol Chem 282:6965–6975.

    Article  PubMed  CAS  Google Scholar 

  • Willimsky, G. and Blankenstein, T. (2005). Sporadic immunogenic tumours avoid destruction by inducing T-cell tolerance. Nature 437:141–146.

    Article  PubMed  CAS  Google Scholar 

  • Yasukawa, H., Misawa, H., Sakamoto, H., Masuhara, M., Sasaki, A., Wakioka, T., Ohtsuka, S., Imaizumi, T., Matsuda, T., Ihle, J. N. and Yoshimura, A. (1999). The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop. EMBO J 18:1309–1320.

    Article  PubMed  CAS  Google Scholar 

  • Yasukawa, H., Ohishi, M., Mori, H., Murakami, M., Chinen, T., Aki, D., Hanada, T., Takeda, K., Akira, S., Hoshijima, M., Hirano, T., Chien, K. and Yoshimura, A. (2003). IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages. Nat Immunol 4:551–556.

    Article  PubMed  CAS  Google Scholar 

  • Yu, H., Kortylewski, M. and Pardoll, D. (2007). Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nat Rev Immunol 7:41–51.

    Article  PubMed  CAS  Google Scholar 

  • Yu, Z., Zhang, W. and Kone, B. (2002). Signal transducers and activators of transcription 3 (STAT3) inhibits transcription of the inducible nitric oxide synthase gene by interacting with nuclear factor kappaB. Biochem J 367:97–105.

    Article  PubMed  CAS  Google Scholar 

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Vicente-Suarez, I., Villagra, A., Sotomayor, E.M. (2008). Signaling Pathways in Antigen-Presenting Cells Involved in the Induction of Antigen-Specific T-Cell Tolerance. 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_9

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