Replicative senescence of CD8 T cells: potential effects on cancer immune surveillance and immunotherapy.
The process of replicative senescence, which stringently limits the proliferative potential of normal T cells, constitutes a potential problem for cancer immunotherapy. The ability of CD8 T cells to recognize and destroy tumor cells has been well-established, but the requirement for massive, prolonged proliferative T-cell expansion and maintenance of functional integrity poses a significant obstacle to the success of cancer immunotherapy. Cancer immune surveillance may also be compromised by the long-term exposure of T cells to tumor antigens, particularly those of latent viruses, which could drive certain T cells to replicative senescence. This review summarizes the major characteristics of T-cell replicative senescence and raises the possibility that this process has the potential to affect both cancer development and treatment. Experimental strategies aimed at preventing T-cell replicative senescence are discussed in the context of cancer immunotherapy and vaccines.
Effros
Rita B
RB
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, 90095-1732, USA. reffros@mednet.ucla.edu
D000951:Antigens, Neoplasm / Q000276:immunology; D018106:CD28 Antigens / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D002455:Cell Division; D016922:Cellular Senescence; D004261:DNA Replication; D004268:DNA-Binding Proteins; D004967:Estrogens / Q000502:physiology; D006801:Humans; D007157:Immunologic Surveillance / Q000276:immunology*; D007167:Immunotherapy; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D019098:Telomerase / Q000502:physiology; D016615:Telomere / Q000502:physiology; D019139:Tumor Escape / Q000276:immunology*
D000951:Antigens, Neoplasm; D018106:CD28 Antigens; D004268:DNA-Binding Proteins; D004967:Estrogens; D019098:Telomerase