PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: Mechanisms, response biomarkers, and combinations

被引：2250

作者：

Zou, Weiping ^{[1
]}

Wolchok, Jedd D. ^{[2
,3
]}

Chen, Lieping ^{[4
]}

机构：

[1] Univ Michigan, Sch Med, Dept Surg, Ann Arbor, MI 48109 USA

[2] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA

[3] Mem Sloan Kettering Canc Ctr, Ludwig Ctr, New York, NY 10065 USA

[4] Yale Univ, Sch Med, Dept Immunobiol, 333 Cedar St, New Haven, CT 06519 USA

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2016年 / 8卷 / 328期

关键词：

REGULATORY T-CELLS; LONG-TERM SAFETY; PROGRAMMED DEATH-1 LIGAND-1; DENDRITIC CELLS; TUMOR MICROENVIRONMENT; CHECKPOINT BLOCKADE; ADVANCED MELANOMA; LUNG-CANCER; PHASE-II; ANTI-PD-L1; ANTIBODY;

D O I：

10.1126/scitranslmed.aad7118

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

PD-L1 and PD-1 (PD) pathway blockade is a highly promising therapy and has elicited durable antitumor responses and long-term remissions in a subset of patients with a broad spectrum of cancers. How to improve, widen, and predict the clinical response to anti-PD therapy is a central theme in the field of cancer immunology and immunotherapy. Oncologic, immunologic, genetic, and biological studies focused on the human cancer microenvironment have yielded substantial insight into this issue. Here, we focus on tumor microenvironment and evaluate several potential therapeutic response markers including the PD-L1 and PD-1 expression pattern, genetic mutations within cancer cells and neoantigens, cancer epigenetics and effector T cell landscape, and microbiota. We further clarify the mechanisms of action of these markers and their roles in shaping, being shaped, and/or predicting therapeutic responses. We also discuss a variety of combinations with PD pathway blockade and their scientific rationales for cancer treatment.

引用

页数：14

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