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T cell tolerance to tumors and cancer immunotherapy

  1. Author:
    Shafer-Weaver, K.
    Anderson, M.
    Malyguine, A.
    Hurwitz, A. A.
  2. Author Address

    NCI, SAIC Frederick Inc, Appl & Dev Res Support Program, Frederick, MD 21701 USA. NIH, Tumor Immun & Tolerance Sect, Lab Mol Immunoregulat, Canc & Inflammat Program,CCR, Frederick, MD USA.;Shafer-Weaver, K, NCI, SAIC Frederick Inc, Appl & Dev Res Support Program, Frederick, MD 21701 USA.;hurwitza@ncifcrf.gov
    1. Year: 2007
  1. Book Title: Immune-Mediated Diseases: From Theory to Therapy
  2. Series Title: Advances in Experimental Medicine and Biology
  3. Springer-Verlag Berlin
  4. Berlin
    1. 601
    2. Pages: 357-368
  5. Type of Work: Book Chapter
  6. ISBN: 0065-2598
  1. Abstract:

    It is widely recognized that the immune system plays a role in cancer progression and that some tumors are inherently immunogenic. The identification of tumor-associated antigens (TAAs) has stimulated research focused on immunotherapies to mediate the regression of established tumors. Cancer-specific immunity has traditionally been aimed at activating CD8(+) cytotoxic T lymphocytes (CTLs) directed against major histocompatibility complex (MHC) class I-binding peptide epitopes. Other approaches utilize T cell adoptive therapy where autologous, tumor-specific T cells propagated in vitro are transferred back into recipients. However, these strategies have met with limited success in part due to the regulatory mechanisms of T cell tolerance, which poses a considerable challenge to cancer immunotherapy. Our laboratory utilizes the TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model, a murine model of prostate cancer, to study mechanisms of T cell tolerization to tumor antigens. We previously demonstrated that upon encounter with their cognate antigen in the tumor microenvironment, naive T cell become tolerized. Our ongoing studies are testing whether provision of CD4(+) T cells can enhance tumor immunity by preventing CD8(+) T cell tolerance. A greater understanding of the interaction between various tumor-specific T cell subsets will facilitate the design of novel approaches to stimulate a more potent antitumor immune response.

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External Sources

  1. WOS: 000248597900038

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