CD8+ T Cell Exhaustion in Cancer

被引：308

作者：

Dolina, Joseph S. ^{[1
]}

Van Braeckel-Budimir, Natalija ^{[1
]}

Thomas, Graham D. ^{[1
]}

Salek-Ardakani, Shahram ^{[1
]}

机构：

[1] Pfizer, Canc Immunol Discovery, San Diego, CA 92121 USA

来源：

FRONTIERS IN IMMUNOLOGY | 2021年 / 12卷

关键词：

T cell exhaustion; PD-1/PD-L1; T cell trafficking; tumor immunity; cancer immunotherapy; CXCR3; co-stimulatory/inhibitory receptors; stem-like CD8(+) T cells; VIRAL PERSISTENCE; EPIGENETIC LANDSCAPE; CHECKPOINT BLOCKADE; PD-1; BLOCKADE; EFFECTOR; ANTIGEN; IMMUNOTHERAPY; RESPONSES; IMMUNITY; STEM;

D O I：

10.3389/fimmu.2021.715234

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

A paradigm shift in the understanding of the exhausted CD8(+) T cell (T-ex) lineage is underway. Originally thought to be a uniform population that progressively loses effector function in response to persistent antigen, single-cell analysis has now revealed that CD8(+) T-ex is composed of multiple interconnected subpopulations. The heterogeneity within the CD8(+) T-ex lineage is comprised of immune checkpoint blockade (ICB) permissive and refractory subsets termed stem-like and terminally differentiated cells, respectively. These populations occupy distinct peripheral and intratumoral niches and are characterized by transcriptional processes that govern transitions between cell states. This review presents key findings in the field to construct an updated view of the spatial, transcriptional, and functional heterogeneity of anti-tumoral CD8(+) T-ex. These emerging insights broadly call for (re-)focusing cancer immunotherapies to center on the driver mechanism(s) underlying the CD8(+) T(ex )developmental continuum aimed at stabilizing functional subsets.

引用

页数：13

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