Inhibitors of the PD-1 Pathway in Tumor Therapy

被引：116

作者：

LaFleur, Martin W. ^{[1
,2
]}

Muroyama, Yuki ^{[3
,4
]}

Drake, Charles G. ^{[4
,5
]}

Sharpe, Arlene H. ^{[1
,6
,7
]}

机构：

[1] Harvard Med Sch, Dept Microbiol & Immunobiol, 77 Ave Louis Pasteur,NRB-837, Boston, MA 02115 USA

[2] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

[3] Johns Hopkins Univ, Sch Med, Dept Oncol, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA

[4] Columbia Univ, Med Ctr, Columbia Ctr Translat Immunol, New York, NY 10032 USA

[5] Columbia Univ, Med Ctr, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA

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

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

来源：

JOURNAL OF IMMUNOLOGY | 2018年 / 200卷 / 02期

基金：

美国国家卫生研究院;

关键词：

CD8(+) T-CELLS; LONG-TERM SAFETY; METASTATIC UROTHELIAL CARCINOMA; OPEN-LABEL; PROGRAMMED DEATH-1; ADVANCED MELANOMA; LUNG-CANCER; SINGLE-ARM; ACQUIRED-RESISTANCE; ANTITUMOR IMMUNITY;

D O I：

10.4049/jimmunol.1701044

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 programmed death 1 (PD-1) pathway delivers inhibitory signals that function as a brake for immune responses. This pathway limits the initiation and duration of immune responses, thereby protecting tissues from immune-mediated damage and autoimmune diseases. However, the PD-1 pathway also inhibits immune responses to tumors. The critical role of PD-1 in preventing antitumor immunity is demonstrated by the transformative effects of PD-1 pathway blockade in a broad range of cancers with the hallmark of durability of response. Despite this success, most patients do not respond to PD-1 monotherapy, and some patients experience adverse events. In this review, we discuss the functions of the PD-1 pathway and its translation to cancer immunotherapy. We also consider current challenges and opportunities for PD-1 cancer immunotherapy, including mechanisms of response and resistance, identification of biomarkers of response to PD-1 therapy, characterization and treatment of PD-1 therapy-related adverse events, and development of safe and effective combination therapies.

引用

页码：375 / 383

页数：9

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