Intratumoral CD4+ T Cells Mediate Anti-tumor Cytotoxicity in Human Bladder Cancer

被引：524

作者：

Oh, David Y. ^{[1
]}

Kwek, Serena S. ^{[1
]}

Raju, Siddharth S. ^{[3
,4
,5
,8
,10
]}

Li, Tony ^{[1
]}

McCarthy, Elizabeth ^{[3
,4
,5
]}

Chow, Eric ^{[6
]}

Aran, Dvir ^{[7
]}

Ilano, Arielle ^{[1
]}

Pai, Chien-Chun Steven ^{[1
,13
]}

Rancan, Chiara ^{[1
]}

Allaire, Kathryn ^{[1
]}

Burra, Arun ^{[1
]}

Sun, Yang ^{[3
,4
,5
]}

Spitzer, Matthew H. ^{[2
,8
,10
]}

Mangul, Serghei ^{[11
]}

Porten, Sima ^{[9
]}

Meng, Maxwell, V ^{[9
]}

Friedlander, Terence W. ^{[1
]}

Ye, Chun Jimmie ^{[2
,3
,4
,5
,7
,12
]}

Fong, Lawrence ^{[1
,2
]}

机构：

[1] Univ Calif San Francisco, Dept Med, Div Hematol Oncol, San Francisco, CA 94143 USA

[2] Univ Calif San Francisco, Parker Inst Canc Immunotherapy, San Francisco, CA 94143 USA

[3] Univ Calif San Francisco, Div Rheumatol, Dept Med, San Francisco, CA 94143 USA

[4] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA

[5] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA

[6] Univ Calif San Francisco, Ctr Adv Technol, Dept Biochem & Biophys, San Francisco, CA 94143 USA

[7] Univ Calif San Francisco, Bakar Computat Hlth Sci Inst, San Francisco, CA 94143 USA

[8] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA

[9] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA

[10] Univ Calif San Francisco, Dept Otolaryngol Head & Neck Surg, San Francisco, CA 94143 USA

[11] Univ Calif Los Angeles, Dept Comp Sci, Los Angeles, CA 90095 USA

[12] Chan Zuckerberg Biohub, San Francisco, CA 94158 USA

[13] Genentech Inc, Dept Oncol Biomarker Dev, 1 DNA Way, San Francisco, CA 94080 USA

来源：

CELL | 2020年 / 181卷 / 07期

关键词：

BREAST-CANCER; BLOCKADE; LYMPHOCYTES; EFFECTOR; MELANOMA; EXPRESSION; LANDSCAPE; MPDL3280A; RESPONSES; IMMUNITY;

D O I：

10.1016/j.cell.2020.05.017

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Responses to anti-PD-1 immunotherapy occur but are infrequent in bladder cancer. The specific T cells that mediate tumor rejection are unknown. T cells from human bladder tumors and non-malignant tissue were assessed with single-cell RNA and paired T cell receptor (TCR) sequencing of 30,604 T cells from 7 patients. We find that the states and repertoires of CD8(+) T cells are not distinct in tumors compared with non-malignant tissues. In contrast, single-cell analysis of CD4(+) T cells demonstrates several tumor-specific states, including multiple distinct states of regulatory T cells. Surprisingly, we also find multiple cytotoxic CD4(+) T cell states that are clonally expanded. These CD4(+) T cells can kill autologous tumors in an MHC class II-dependent fashion and are suppressed by regulatory T cells. Further, a gene signature of cytotoxic CD4(+) T cells in tumors predicts a clinical response in 244 metastatic bladder cancer patients treated with anti-PD-L1.

引用

页码：1612 / +

页数：27

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