Defining 'T cell exhaustion'

被引：1056

作者：

Blank, Christian U. ^{[1
]}

Haining, W. Nicholas ^{[2
]}

Held, Werner ^{[3
]}

Hogan, Patrick G. ^{[4
,5
]}

Kallies, Axel ^{[6
]}

Lugli, Enrico ^{[7
]}

Lynn, Rachel C. ^{[8
]}

Philip, Mary ^{[10
,11
]}

Rao, Anjana ^{[12
,13
]}

Restifo, Nicholas P. ^{[9
]}

Schietinger, Andrea ^{[14
]}

Schumacher, Ton N. ^{[1
]}

Schwartzberg, Pamela L. ^{[15
]}

Sharpe, Arlene H. ^{[16
]}

Speiser, Daniel E. ^{[3
]}

Wherry, E. John ^{[17
]}

Youngblood, Benjamin A. ^{[18
]}

Zehn, Dietmar ^{[19
]}

机构：

[1] Netherlands Canc Inst, Amsterdam, Netherlands

[2] Merck Res Labs, Discovery Oncol, Boston, MA USA

[3] Univ Lausanne, Dept Oncol, Lausanne, Switzerland

[4] La Jolla Inst Immunol, La Jolla, CA USA

[5] Univ Calif San Diego, San Diego, CA 92103 USA

[6] Univ Melbourne, Peter Doherty Inst Infect & Immun, Dept Microbiol & Immunol, Melbourne, Vic, Australia

[7] Humanitas Clin & Res Ctr, Lab Translat Immunol & Humanitas Flow Cytometry C, Rozzano, Italy

[8] Lyell Immunopharma, Res, San Francisco, CA USA

[9] Lyell Immunopharma, San Francisco, CA USA

[10] Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol & Oncol, Nashville, TN USA

[11] Vanderbilt Univ, Med Ctr, Dept Pathol Microbiol & Immunol, Nashville, TN USA

[12] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA

[13] Moores Canc Ctr, La Jolla, CA USA

[14] Mem Sloan Kettering Canc Ctr, Immunol Program, 1275 York Ave, New York, NY 10021 USA

[15] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[16] Harvard Med Sch, Blavatnik Inst, Dept Immunol, Boston, MA 02115 USA

[17] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA

[18] St Jude Childrens Res Hosp, Dept Immunol, 332 N Lauderdale St, Memphis, TN 38105 USA

[19] Tech Univ Munich, Sch Life Sci Weihenstephan, Div Anim Physiol & Immunol, Freising Weihenstephan, Germany

来源：

NATURE REVIEWS IMMUNOLOGY | 2019年 / 19卷 / 11期

关键词：

VIRUS-INFECTION; PD-1; PERSISTENCE; DIFFERENTIATION; IMMUNOTHERAPY; AUTOIMMUNITY; DYSFUNCTION; SUBSETS; CANCER; LIMITS;

D O I：

10.1038/s41577-019-0221-9

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

'T cell exhaustion' is a broad term that has been used to describe the response of T cells to chronic antigen stimulation, first in the setting of chronic viral infection but more recently in response to tumours. Understanding the features of and pathways to exhaustion has crucial implications for the success of checkpoint blockade and adoptive T cell transfer therapies. In this Viewpoint article, 18 experts in the field tell us what exhaustion means to them, ranging from complete lack of effector function to altered functionality to prevent immunopathology, with potential differences between cancer and chronic infection. Their responses highlight the dichotomy between terminally differentiated exhausted T cells that are TCF1(-) and the self-renewing TCF1(+) population from which they derive. These TCF1(+) cells are considered by some to have stem cell-like properties akin to memory T cell populations, but the developmental relationships are unclear at present. Recent studies have also highlighted an important role for the transcriptional regulator TOX in driving the epigenetic enforcement of exhaustion, but key questions remain about the potential to reverse the epigenetic programme of exhaustion and how this might affect the persistence of T cell populations.

引用

页码：665 / 674

页数：10

共 65 条

[1] CD4+ T Cell Help Confers a Cytotoxic T Cell Effector Program Including Coinhibitory Receptor Downregulation and Increased Tissue Invasiveness [J].