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Sci Transl Med. 2016 Mar 2;8(328):328rv4. doi: 10.1126/scitranslmed.aad7118.

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

Author information

1
Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA. wzou@med.umich.edu wolchokj@mskcc.org lieping.chen@yale.edu.
2
Department of Medicine and the Ludwig Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. wzou@med.umich.edu wolchokj@mskcc.org lieping.chen@yale.edu.
3
Department of Immunobiology, Yale University School of Medicine, New Haven CT 06519, USA. wzou@med.umich.edu wolchokj@mskcc.org lieping.chen@yale.edu.

Abstract

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.

PMID:
26936508
PMCID:
PMC4859220
DOI:
10.1126/scitranslmed.aad7118
[Indexed for MEDLINE]
Free PMC Article

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