Phenotypic plasticity and reduced tissue retention of exhausted tumor-infiltrating T cells following neoadjuvant immunotherapy in head and neck cancer

被引：30

作者：

Sievers, Cem ^{[1
]}

Craveiro, Marco ^{[1
]}

Friedman, Jay ^{[1
]}

Robbins, Yvette ^{[1
]}

Yang, Xinping ^{[1
]}

Bai, Ke ^{[1
]}

Nguyen, Andy ^{[2
]}

Redman, Jason M. ^{[3
]}

Chari, Raj ^{[4
]}

Soon-Shiong, Patrick ^{[2
]}

Schlom, Jeffrey ^{[3
]}

Gulley, James ^{[3
]}

Allen, Clint T. ^{[1
,3
]}

机构：

[1] NIA, NCI, Ctr Canc Res, Surg Oncol Program,Head & Neck Sect, Bethesda, MD 20892 USA

[2] ImmunityBio, Culver City, CA USA

[3] NIA, NCI, Ctr Immuno Oncol, Ctr Canc Res, Bethesda, MD 20892 USA

[4] Frederick Natl Lab Canc Res, Lab Anim Sci Program, Genome Modificat Core, Frederick, MD USA

来源：

CANCER CELL | 2023年 / 41卷 / 05期

基金：

美国国家卫生研究院;

关键词：

RESPONSES; BLOCKADE; MELANOMA;

D O I：

10.1016/j.ccell.2023.03.014

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Neoadjuvant immunotherapies (NITs) have led to clinical benefits in several cancers. Characterization of the molecular mechanisms underlying responses to NIT may lead to improved treatment strategies. Here we show that exhausted, tumor-infiltrating CD8+ T (Tex) cells display local and systemic responses to concurrent neo-adjuvant TGF-0 and PD-L1 blockade. NIT induces a significant and selective increase in circulating Tex cells associated with reduced intratumoral expression of the tissue-retention marker CD103. TGF-0-driven CD103 expression on CD8+T cells is reversed following TGF-0 neutralization in vitro, implicating TGF-0 in T cell tissue retention and impaired systemic immunity. Transcriptional changes implicate T cell receptor signaling and glutamine metabolism as important determinants of enhanced or reduced Tex treatment response, respec-tively. Our analysis illustrates physiological and metabolic changes underlying T cell responses to NIT, high-lighting the interplay between immunosuppression, tissue retention, and systemic anti-tumor immunity and suggest antagonism of T cell tissue retention as a promising neoadjuvant treatment strategy.

引用

页码：887 / +

页数：22

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