Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 130, Issue 3, Pages 1073-1083Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI133679
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Funding
- American Cancer Society [RSG-10-160-01-LIB]
- Melanoma Research Alliance
- NIH [AI097852, AI094478, CA184379]
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The functional state of the preexisting T cells in the tumor microenvironment is a key determinant for effective antitumor immunity and immunotherapy. Increasing evidence suggests that immunosenescence is an important state of T cell dysfunction that is distinct from exhaustion, a key strategy used by malignant tumors to evade immune surveillance and sustain the suppressive tumor microenvironment. Here, we discuss the phenotypic and functional characteristics of senescent T cells and their role in human cancers. We also explore the possible mechanisms and signaling pathways responsible for induction of T cell senescence by malignant tumors, and then discuss potential strategies to prevent and/or reverse senescence in tumor-specific T cells. A better understanding of these critical issues should provide novel strategies to enhance cancer immunotherapy.
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