Biomarkers of therapeutic response with immune checkpoint inhibitors

Abstract

Immune checkpoint inhibitors (ICPIs) have revolutionized the treatment paradigm of a wide range of malignancies with durable responses seen in even advanced, refractory cancers. Unfortunately, only a small proportion of patients with cancer derive meaningful benefit to ICPI therapy, and its use is also limited by significant immune and financial toxicities. Thus, there is a critical need for the development of biomarkers to reliably predict response to ICPI therapy. Only a few biomarkers are validated and approved for use with currently Food and Drug administration (FDA)-approved ICPIs. The development and broad application of biomarkers is limited by the lack of complete understanding of the complex interactions of tumor-host environment, the effect of immunotherapies on these already complex interactions, a lack of standardization and interpretation of biomarker assays across tumor types. Despite these challenges, the field of identifying predictive biomarkers is evolving at an unprecedented pace leaving the clinician responsible for identifying the patients that may derive optimal benefit from ICPIs. In this review, we provide clinicians with a current and practical update on the key, clinically relevant biomarkers of response to ICPIs. We categorize the current and emerging biomarkers of response to ICPIs in four major categories that govern anticancer response-the inflamed tumor, tumor antigens, immune suppression, and overall host environment.

Keywords: Biomarker; immune checkpoint inhibitors (ICPIs); predictive; prognostic.

Figure 1

Current and emerging biomarkers of response to immune checkpoint inhibitors categorized based on elements of cancer immunity. TMB, Tumor mutational burden; MSI-H, Microsatellite instability-High; dMMR, Deficient mismatch repair; LAG-3, Lymphocyte activation gene 3; IDO-1, Indoleamine 2.3-dioxygenase; Tregs, Regulatory T-cells; PD-L1, Programmed death ligand-1; PD-L2, Programmed death ligand-2.