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T Cell Senescence and Tumor Immunotherapy

  • Xia Liu
  • Guangyong Peng
Living reference work entry

Abstract

Defining molecular mechanisms involved in immune tolerance in antitumor immunity is critical for the development of novel therapeutic strategies against cancer. Increasing evidence suggests that the development of senescence in tumor-experienced effector T cells is a general feature utilized by malignant tumors to escape immune surveillance and sustain the tumor-suppressive microenvironment. However, very limited information is known about the molecular mechanisms responsible for the induction of T cell senescence and its functional role within the tumor microenvironment, although cellular senescence has been identified as a biological process more than 50 years ago. In addition, the development of effective strategies to prevent the generation and/or functional rejuvenation of senescent tumor-specific T cells is urgently needed for successful antitumor immunity and tumor immunotherapy in clinical treatment. Here we summarize current knowledge regarding the development and functional role of senescent T cells in human cancers. In particular, we emphasize several recently identified phenotypic and functional characteristics of senescent T cells in cancer patients, potential mechanisms for their development and generation, and possible molecular strategies for prevention and regulation of these effects in the tumor microenvironment. Improved understanding of these issues is critical in order to elucidate the role of senescent T cells in antitumor immunity and should open new avenues for cancer immunotherapy specifically targeting senescent T cells.

Keywords

Immunosenescence Regulatory T cells Tumor microenvironment Toll-like receptor cAMP Tumor immunotherapy 

Notes

Acknowledgments

Due to space limitations, the authors apologize that they cannot cite all relevant references in this research area. This work was partially supported by grants from the American Cancer Society (RSG-10-160-01-LIB, to G. P), Melanoma Research Alliance (to G. P), and the NIH (AI097852, AI094478, and CA184379 to G. P).

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Infectious Diseases, Allergy & ImmunologySaint Louis University School of MedicineSt. LouisUSA
  2. 2.Department of Internal MedicineSaint Louis UniversitySt. LouisUSA

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