Circulating biomarkers of response to immunotherapy and immune-related adverse events

ABSTRACT

Introduction

Immune checkpoint blockade has revolutionized cancer treatment. However, response rates vary, and these treatments have a high rate of immune-related side effects, which can be limiting. Thus, tests to predict who will respond and who may experience side effects are of critical importance toward realizing the ultimate goal of precision oncology.

Areas Covered

We review several of the most recent advances in circulating biomarkers that have been reported to be useful in predicting response and immune-related adverse events (irAE) to checkpoint blockade immunotherapies (CBI). We focus on high-quality studies published within the last few years. We highlight significant findings, identify areas for improvement, and provide recommendations on how these biomarkers may be translated into clinical utility.

Expert Opinion

As newer immunotherapies are developed, there is a pressing need to identify circulating biomarkers that can help predict responses and side effects. Current studies are mostly small-scale and retrospective; there is a need for larger-scale and prospective studies to help validate several of the biomarkers detailed here. As oncology focuses more on precision-based approaches, it is likely that a combination of biomarkers, including circulating ones as detailed here, will have critical utility in guiding clinical decisions.

KEYWORDS:

• Cancer immunotherapy
• circulating biomarkers
• PD-1
• PD-L1
• immune-related adverse events
• precision medicine

Article highlights

• Immune therapy treatments targeting specific checkpoints have become the new standard of care for many cancers

• Mixed response rates have made biomarkers for predicting treatment and survival outcomes extremely valuable

• Many circulating biomarkers (ctDNA, miRNAs, S100 proteins, C-reactive protein, TCR repertoires) have been recently identified as predictive of immune therapy response

• Immune therapy-induced irAEs are primary causes of treatment discontinuation

• Various biomarkers (IL cytokines, CXCL5/CD163, blood cell counts, autoantibodies, TCR repertoires, gut microbiome) have been putatively associated with irAEs

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewers disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

RPK acknowledges funding from the Cancer Research Institute, Clinic and Laboratory Integration Program (CLIP), the American Cancer Society grant nos. 129523-MRSG-16-029-01-DDC and TLC-21-003-01-TLC, Department of Defense CDMRP grant numbers W81XWH-17-1-0514 and W81XWH-17-1-0098, Melanoma Research Alliance grant number 344442, the OHSU Physician-Scientist Program, and the Cancer Early Detection Advanced Research Center (CEDAR) of Knight Cancer Institute at OHSU..