Rescue of exhausted CD8 T cells by PD-1-targeted therapies is CD28-dependent

被引：765

作者：

Kamphorst, Alice O. ^{[1
]}

Wieland, Andreas ^{[1
]}

Nasti, Tahseen ^{[1
]}

Yang, Shu ^{[1
,2
,13
]}

Zhang, Ruan ^{[3
,4
]}

Barber, Daniel L. ^{[1
,5
]}

Konieczny, Bogumila T. ^{[1
]}

Daugherty, Candace Z. ^{[1
]}

Koenig, Lydia ^{[6
]}

Yu, Ke ^{[6
]}

Sica, Gabriel L. ^{[7
]}

Sharpe, Arlene H. ^{[8
,9
,10
]}

Freeman, Gordon J. ^{[11
]}

Blazar, Bruce R. ^{[12
]}

Turka, Laurence A. ^{[3
,4
]}

Owonikoko, Taofeek K. ^{[6
]}

Pillai, Rathi N. ^{[6
]}

Ramalingam, Suresh S. ^{[6
]}

Araki, Koichi ^{[1
]}

Ahmed, Rafi ^{[1
]}

机构：

[1] Emory Univ, Sch Med, Emory Vaccine Ctr, Dept Microbiol & Immunol, Atlanta, GA 30322 USA

[2] Cent S Univ, Xiangya Sch Med, Changsha 410013, Hunan, Peoples R China

[3] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02144 USA

[4] Harvard Med Sch, Boston, MA 02144 USA

[5] NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA

[6] Emory Univ, Sch Med, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA

[7] Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA

[8] Harvard Med Sch, Dept Microbiol & Immunol, Boston, MA 02115 USA

[9] Harvard Med Sch, Evergrande Ctr Immunol Dis, Boston, MA 02115 USA

[10] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA

[11] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[12] Univ Minnesota, Dept Pediat, Div Blood & Marrow Transplantat, Minneapolis, MN 55455 USA

[13] Tianjin Med Univ, Gen Hosp, Dept Neurol, Tianjin 300052, Peoples R China

来源：

SCIENCE | 2017年 / 355卷 / 6332期

基金：

美国国家卫生研究院;

关键词：

CHRONIC VIRAL-INFECTION; RESPONSES; IMMUNITY; CANCER; PD-1; COSTIMULATION; BLOCKADE; EFFECTOR; MEMORY;

D O I：

10.1126/science.aaf0683

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Programmed cell death-1 (PD-1)-targeted therapies enhance T cell responses and show efficacy in multiple cancers, but the role of costimulatory molecules in this T cell rescue remains elusive. Here, we demonstrate that the CD28/B7 costimulatory pathway is essential for effective PD-1 therapy during chronic viral infection. Conditional gene deletion showed a cell-intrinsic requirement of CD28 for CD8 T cell proliferation after PD-1 blockade. B7-costimulation was also necessary for effective PD-1 therapy in tumor-bearing mice. In addition, we found that CD8 T cells proliferating in blood after PD-1 therapy of lung cancer patients were predominantly CD28-positive. Taken together, these data demonstrate CD28-costimulation requirement for CD8 T cell rescue and suggest an important role for the CD28/B7 pathway in PD-1 therapy of cancer patients.

引用

页码：1423 / 1427

页数：5

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