PD-L1 (B7-H1) and PD-1 Pathway Blockade for Cancer Therapy: Mechanisms, Response Biomarkers and Combinations

By W. Zou, J. Wolchok, Lieping Chen. Science Translational Medicine, 2016

2,193 citations recorded by the source corpus.

PD pathway blockade elicits durable antitumor responses in a subset of patients with a broad spectrum of cancers. Gloss 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. 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.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/cba390a5b67c8009a2ac84cdca40a2803b266103

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Citations in the corpus

Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by Modulating Autophagy (2017, background): “Unfortunately, CRC patients are generally not responsive to novel immune checkpoint therapy (Zou et al., 2016).”
Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer (2017, background): “The PD-1 receptor on cytotoxic T cells suppresses their activity when bound by its ligands PD-L1 or PD-L2 (2,3).”
A transcriptionally and functionally distinct PD-1+ CD8+ T cell pool with predictive potential in non-small cell lung cancer treated with PD-1 blockade (2018, neutral): “5 (2D1), -CD56 PE (CMSSB), - CD3 APC-eFluor780 (SK7), -Lag-3 FITC (3DS223H), -TIGIT PE (MBSA43), -2B4 FITC (eBioDM244), -CD137 FITC (4B4), -IL-2 PE (MQ1-17H12), -TNF-α APC (MAb11), - CD26 FITC (2A6), -CXCR5 Biotin (MU5UBEE), -ICOS FITC (ISA-3), -CD38 APC (HIT2), -Eomes eFluor660 (WD1928), -T-bet PE ”