Coinhibitory Pathways in Immunotherapy for Cancer

被引：703

作者：

Baumeister, Susanne H. ^{[1
,2
,3
,4
]}

Freeman, Gordon J. ^{[1
,4
]}

Dranoff, Glenn ^{[1
,5
]}

Sharpe, Arlene H. ^{[6
,7
]}

机构：

[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA

[2] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA

[3] Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Boston, MA 02115 USA

[5] Novartis Inst BioMed Res, Exploratory Immunooncol, Cambridge, MA 02139 USA

[6] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA

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

来源：

ANNUAL REVIEW OF IMMUNOLOGY, VOL 34 | 2016年 / 34卷

关键词：

tumor immunity; cancer immunotherapy; CTLA-4; PD-1; PD-L1; PHASE-I TRIAL; REGULATORY T-CELLS; LYMPHOCYTE-ASSOCIATED ANTIGEN-4; RESISTANT PROSTATE-CANCER; COLONY-STIMULATING FACTOR; MEDIATED CYTOTOXIC IMMUNOTHERAPY; CTLA-4; BLOCKADE; MONOCLONAL-ANTIBODY; ANTITUMOR IMMUNITY; PD-1;

D O I：

10.1146/annurev-immunol-032414-112049

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The immune system is capable of recognizing tumors and eliminates many early malignant cells. However, tumors evolve to evade immune attack, and the tumor microenvironment is immunosuppressive. Immune responses are regulated by a number of immunological checkpoints that promote protective immunity and maintain tolerance. T cell coinhibitory pathways restrict the strength and duration of immune responses, thereby limiting immune-mediated tissue damage, controlling resolution of inflammation, and maintaining tolerance to prevent autoimmunity. Tumors exploit these coinhibitory pathways to evade immune eradication. Blockade of the PD-1 and CTLA-4 checkpoints is proving to be an effective and durable cancer immunotherapy in a subset of patients with a variety of tumor types, and additional combinations are further improving response rates. In this review we discuss the immunoregulatory functions of coinhibitory pathways and their translation to effective immunotherapies for cancer.

引用

页码：539 / 573

页数：35

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