Circulating tumor-reactive KIR+CD8+ T cells suppress anti-tumor immunity in patients with melanoma

被引：1

作者：

Lu, Benjamin Y. ^{[1
,2
]}

Lucca, Liliana E. ^{[2
,14
]}

Lewis, Wesley ^{[3
,4
]}

Wang, Jiping ^{[5
]}

Nogueira, Catarina V. ^{[6
]}

Heer, Sebastian ^{[7
]}

Rayon-Estrada, Violeta ^{[6
]}

Axisa, Pierre-Paul ^{[2
,14
]}

Reeves, Sarah M. ^{[8
]}

Buitrago-Pocasangre, Nicholas C. ^{[2
]}

Pham, Giang H. ^{[2
]}

Kojima, Mina L. ^{[9
]}

Wei, Wei ^{[1
]}

Aizenbud, Lilach ^{[1
]}

Bacchiocchi, Antonietta ^{[10
]}

Zhang, Lin ^{[1
]}

Walewski, Joseph J. ^{[2
]}

Chiang, Veronica ^{[11
]}

Olino, Kelly ^{[12
]}

Clune, James ^{[12
]}

Halaban, Ruth ^{[10
]}

Kluger, Yuval ^{[4
,5
]}

Coyle, Anthony J. ^{[6
]}

Kisielow, Jan ^{[7
]}

Obermair, Franz-Josef ^{[7
]}

Kluger, Harriet M. ^{[1
]}

Hafler, David A. ^{[2
,8
,13
]}

机构：

[1] Yale Sch Med, Dept Med, New Haven, CT 06510 USA

[2] Yale Sch Med, Dept Neurol, New Haven, CT 06510 USA

[3] Yale Univ, Interdept Program Computat Biol & Bioinformat, New Haven, CT USA

[4] Yale Sch Med, Dept Pathol, New Haven, CT USA

[5] Yale Univ, Appl Math Program, New Haven, CT USA

[6] Repertoire Immune Med, Cambridge, MA USA

[7] Repertoire Immune Med, Schlieren, Switzerland

[8] Yale Sch Med, Dept Immunobiol, New Haven, CT 06510 USA

[9] Yale Sch Med, Dept Genet, New Haven, CT USA

[10] Yale Sch Med, Dept Dermatol, New Haven, CT USA

[11] Yale Sch Med, Dept Neurosurg, New Haven, CT USA

[12] Yale Sch Med, Dept Surg, New Haven, CT USA

[13] MIT & Harvard Univ, Broad Inst, Cambridge, MA 02139 USA

[14] Univ Toulouse, Univ Toulouse III Paul Sabatier, CNRS, Inserm,Canc Res Ctr Toulouse, Toulouse, France

来源：

NATURE IMMUNOLOGY | 2025年 / 26卷 / 01期

基金：

美国国家卫生研究院;

关键词：

MOLECULAR SIGNATURES; EXPRESSION; LYMPHOCYTES; RECEPTOR; IMMUNOTHERAPY; CANCER; LASSO;

D O I：

10.1038/s41590-024-02023-4

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Effective anti-tumor immunity is driven by cytotoxic CD8+ T cells with specificity for tumor antigens. However, the factors that control successful tumor rejection are not well understood. Here we identify a subpopulation of CD8+ T cells that are tumor-antigen-specific and can be identified by KIR expression but paradoxically impair anti-tumor immunity in patients with melanoma. These tumor-antigen-specific KIR+CD8+ regulatory T cells target other tumor-antigen-specific CD8+ T cells, can be detected in both the tumor and the blood, have a conserved transcriptional program and are associated with a poor overall survival. These findings broaden our understanding of the transcriptional and functional heterogeneity of human CD8+ T cells and implicate KIR+CD8+ regulatory T cells as a cellular mediator of immune evasion in human cancer. Tumor-antigen-specific CD8+ T cells are generally thought to help fight against cancer, but here the authors identify a subpopulation of CD8+ T cells that are associated with a poor clinical outcome in melanoma. Although these cells can recognize tumor antigens, they suppress cancer immunity.

引用

页码：82 / 91

页数：30

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