Mechanisms of T cell tolerance and suppression in cancer mediated by tumor-associated antigens and hormones.
Despite recent advances in vaccine technology, vaccines designed to elicit T cell-based anti-tumor immunity have only achieved partial success in the clinic. The underlying reason probably stems in part from the ability of tumors to repress cognate T cell responses, which appears to operate at two separate levels. In some cases, tumors engage a variety of immunosuppressive pathways that inhibit primed effector T cells from functioning when they enter the tumor microenvironment. Some of these immunosuppressive mechanisms include the production of cytokines such as TGF-beta and the recruitment or differentiation of regulatory T cells. In contrast, other types of tumors induce a systemic impairment in the function of tumor-reactive T cells (i.e., tolerance). Tolerance to tumor antigens can be mediated through the same mechanisms that induce T cell tolerance to normal self-antigens in order to avoid autoimmunity, and can develop not only towards differentiation antigens that are expressed on both tumors as well as on the normal tissues from which they derive, but can also develop rapidly towards tumor-specific antigens. Additionally, both naive and effector T cells are susceptible to tolerization, suggesting that tolerance can potentially dampen both the priming and effector phases of anti-tumor T cell responses. Certain hormones can influence both tumorigenesis as well as T cell function and tolerance, and thus hormonal therapies could potentially impact the efficacy of T cell-based therapies. An example of this type of interaction that will be discussed in detail is the relationship between androgens and prostate cancer.
Adler
Adam J
AJ
Center for Immunotherapy of Cancer and Infectious Diseases and Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030-1601, USA. aadler@up.uchc.edu
D000728:Androgens / Q000502:physiology; D000951:Antigens, Neoplasm / Q000502:physiology*; D001324:Autoantigens / Q000276:immunology; D006728:Hormones / Q000502:physiology*; D006801:Humans; D007108:Immune Tolerance; D008297:Male; D009369:Neoplasms / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000728:Androgens; D000951:Antigens, Neoplasm; D001324:Autoantigens; D006728:Hormones