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Next generation predictive biomarkers for immune checkpoint inhibition

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Abstract

With the advent of targeted therapies, there has been a revolution in the treatment of cancer across multiple histologies. Immune checkpoint blockade has made it possible to take advantage of receptor-ligand interactions between immune and tumor cells in a wide spectrum of malignancies. Toxicity in healthy tissue, however, can limit our use of these agents. Immune checkpoint blockade has been approved in advanced melanoma, renal cell cancer, non-small cell lung cancer, relapsed refractory Hodgkin’s lymphoma, and urothelial cancer. Though FDA-approved indications for use of some of these novel agents depend on current protein-based programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) assays, detection methods come with several caveats. Additional predictive tools must be interrogated to discern responders from non-responders. Some of these include measurement of microsatellite instability, PD-L1 amplification, cluster of differentiation 8 (CD8) infiltrate density, and tumor mutational burden. This review serves to synthesize biomarker detection at the DNA, RNA, and protein level to more accurately forecast benefit from these novel agents.

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Acknowledgments

Yulian Khagi, MD, Razelle Kurzrock, MD, and Sandip Patel, MD, completed the compilation of references, writing, editing, and proofreading of this article. There were no additional parties involved in the completion of this work. This research was funded in part by National Cancer Institute grant P30 CA016672.

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  1. Center for Personalized Cancer Therapy, Division of Hematology and Oncology, University of California San Diego Moores Cancer Center, 3855 Health Sciences Dr., La Jolla, CA, 92093, USA

    Yulian Khagi, Razelle Kurzrock & Sandip Pravin Patel

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Dr. Khagi has no conflicts of interest. Dr. Patel receives research funding from MedImmune, Genentech, Pfizer, Amgen, Xcovery, Lilly, and Bristol-Myers Squibb. Dr. Kurzrock receives research funding from Genentech, Merck Serono, Pfizer, Sequenom, Foundation Medicine, and Guardant.

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Dr. Khagi has no financial disclosures to report. Dr. Patel receives speaking fees from Boehringer Ingelheim and Merck. Dr. Kurzrock receives consultant and advisory board fees from Actuate Therapeutics and Xbiotech. She has an ownership interest in Novena Inc. and Curematch Inc. Dr. Kurzrock is funded in part by the Joan and Irwin Jacobs philanthropic fund.

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Khagi, Y., Kurzrock, R. & Patel, S.P. Next generation predictive biomarkers for immune checkpoint inhibition. Cancer Metastasis Rev 36, 179–190 (2017). https://doi.org/10.1007/s10555-016-9652-y

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  • DOI: https://doi.org/10.1007/s10555-016-9652-y

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