T cell tolerance to tumors and cancer immunotherapy.
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.
Shafer-Weaver
Kimberly
K
Applied and Developmental Research Support Program, SAIC-Frederick, Inc., NCI-Frederick, Frederick, MD, USA.
Anderson
Michael
M
Malyguine
Anatoli
A
Hurwitz
Arthur A
AA
D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry; D000939:Epitopes / Q000737:chemistry; D006801:Humans; D007107:Immune System / Q000502:physiology*; D007108:Immune Tolerance; D007167:Immunotherapy / Q000379:methods*; D008285:Major Histocompatibility Complex; D008297:Male; D051379:Mice; D008954:Models, Biological; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D011471:Prostatic Neoplasms / Q000276:immunology
D000951:Antigens, Neoplasm; D000939:Epitopes