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Cancer Immunol Immunother. 2004 Oct;53(10):925-33. Epub 2004 Apr 6.

Replicative senescence of CD8 T cells: potential effects on cancer immune surveillance and immunotherapy.

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  • 1Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, 90095-1732, USA.


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.

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