Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy

被引：2513

作者：

Topalian, Suzanne L. ^{[1
,2
]}

Taube, Janis M. ^{[2
,3
,4
,5
]}

Anders, Robert A. ^{[2
,5
]}

Pardoll, Drew M. ^{[2
,4
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Dept Surg, 1550 Orleans St,CRB2 Room 508, Baltimore, MD 21287 USA

[2] Johns Hopkins Univ, Sch Med, Bloomberg Kimmel Inst Canc Immunotherapy, 1550 Orleans St,CRB2 Room 508, Baltimore, MD 21287 USA

[3] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Dept Dermatol, 1550 Orleans St,CRB2 Room 508, Baltimore, MD 21287 USA

[4] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, 1550 Orleans St,CRB2 Room 508, Baltimore, MD 21287 USA

[5] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Dept Pathol, 1550 Orleans St,CRB2 Room 508, Baltimore, MD 21287 USA

来源：

NATURE REVIEWS CANCER | 2016年 / 16卷 / 05期

关键词：

ADVANCED MELANOMA PATIENTS; MERKEL CELL POLYOMAVIRUS; LONG-TERM SURVIVAL; EPSTEIN-BARR-VIRUS; REGULATORY T-CELLS; CTLA-4; BLOCKADE; PD-1; HUMAN-PAPILLOMAVIRUS; ANTICANCER IMMUNOTHERAPY; TUMOR MICROENVIRONMENT;

D O I：

10.1038/nrc.2016.36

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

With recent approvals for multiple therapeutic antibodies that block cytotoxic Tylymphocyte associated antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) in melanoma, non-small-cell lung cancer and kidney cancer, and additional immune checkpoints being targeted clinically, many questions still remain regarding the optimal use of drugs that block these checkpoint pathways. Defining biomarkers that predict therapeutic effects and adverse events is a crucial mandate, highlighted by recent approvals for two PDL1 diagnostic tests. Here, we discuss biomarkers for anti-PD1 therapy based on immunological, genetic and virological criteria. The unique biology of the CTLA4 immune checkpoint, compared with PD1, requires a different approach to biomarker development. Mechanism-based insights from such studies may guide the design of synergistic treatment combinations based on immune checkpoint blockade.

引用

页码：275 / 287

页数：13

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