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Review
. 2018 Jan 15;200(2):375-383.
doi: 10.4049/jimmunol.1701044.

Inhibitors of the PD-1 Pathway in Tumor Therapy

Martin W LaFleur  1   2 , Yuki Muroyama  3   4 , Charles G Drake  5   6 , Arlene H Sharpe  7   8
Affiliations
Review

Inhibitors of the PD-1 Pathway in Tumor Therapy

Martin W LaFleur et al. J Immunol. .

Abstract

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.

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Conflict of interest statement

Disclosures

A.H.S. has served as a paid consultant for Novartis, Surface Oncology, SQZ Biotechnologies, and Adaptimmune and has patents on the PD-1 pathway licensed by Roche and Novartis. C.G.D. has served as a paid consultant to Bristol-Myers Squibb, Compugen, Roche/Genentech, Regeneron, AstraZeneca/Medimmune, and Merck and is a coinventor on patents licensed from Johns Hopkins to AstraZeneca/Medimmune and to Bristol-Myers Squibb. The other authors have no financial conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Timeline for basic and clinical development of PD-1/PD-L1 targeted cancer immunotherapy. Upper timeline, Preclinical studies. Lower/magnified timeline, FDA approvals.
See this image and copyright information in PMC

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