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Exhaustion and senescence: two crucial dysfunctional states of T cells in the tumor microenvironment.

Abstract：

:The failure of a massive influx of tumor-infiltrating T lymphocytes to eradicate tumor cells in the tumor microenvironment is mainly due to the dysfunction of T cells hyporesponsive to tumors. T-cell exhaustion and senescence induced by malignant tumors are two important dysfunctional states that coexist in cancer patients, hindering effective antitumor immunity and immunotherapy and sustaining the suppressive tumor microenvironment. Although exhausted and senescent T cells share a similar dysfunctional role in antitumor immunity, they are distinctly different in terms of generation, development, and metabolic and molecular regulation during tumor progression. Here, we discuss the unique phenotypic and functional characteristics of these two types of dysfunctional T cells and their roles in tumor development and progression. In addition, we further discuss the potential molecular and metabolic signaling pathways responsible for the control of T-cell exhaustion and senescence in the suppressive tumor microenvironment. Understanding these critical and fundamental features should facilitate rethinking the unresponsiveness to current immunotherapies in clinical patients and lead to further development of novel and effective strategies that target different types of dysfunctional T cells to enhance cancer immunotherapy.

journal_name

Cell Mol Immunol

journal_title

Cellular & molecular immunology

authors

Zhao Y,Shao Q,Peng G

doi

10.1038/s41423-019-0344-8

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

27-35

issue

1

eissn

1672-7681

issn

2042-0226

pii

10.1038/s41423-019-0344-8

journal_volume

17

pub_type

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