Research progress and clinical application of predictive biomarker for immune checkpoint inhibitors

ABSTRACT

Introduction: Immune checkpoint inhibitors (ICIs) have emerged as epochal milestones in the field of anti-cancer immunotherapy. With promising clinical effectiveness, ICIs can significantly prolong the overall survival of patients with advanced cancer of different types. Although their remarkable effectiveness has been demonstrated in clinical application, ICIs display limitations in terms of unique response patterns. Only a subset of patients exhibits objective responses, while others show rapid disease progression. Considering that there is a fair representation of both subsets of patients (responders and non-responders), clinicians ought to effectively stratify patients who will potentially benefit from ICI therapy, and optimize a strategy for patient selection.

Areas covered: In this review, the authors have summarized several key factors involved in the biomarker development of ICI therapy, such as neoantigen production and presentation, the tumor microenvironment, and alternation in specific gene signaling pathways.

Expert opinion: Considering the extreme complexity of the immune system, a single biomarker may fail to appropriately stratify patients for ICI therapy. Therefore, future biomarker research should focus on designing an integrated biomarker system that will successfully guide combination therapies to overcome resistance to immunotherapy.

KEYWORDS:

• Predictive biomarker
• immune checkpoint inhibitors
• tumor microenvironment
• programmed cell death protein 1
• cytotoxic T-lymphocyte-associated protein 4

Article highlights

• Although immune checkpoint inhibitors have attained great success in clinical practice, some clinical challenges still exist during treatment, such as efficacy differences at the individual level, and immune-related adverse effects. Therefore, predictive biomarkers are largely required for anticipating the efficacy of immune checkpoint inhibitors.

• Several key factors regarding biomarker development for ICI therapy are summarized, such as neoantigen production and presentation, the tumor microenvironment, and alternation in specific gene signaling pathways.

• Tumor microenvironment-related factors are discussed, such as PD-L1 expression, tumor infiltrating lymphocytes, indoleamine-2,3-dioxygenase, interferon signaling pathways, regulatory T cell, and myeloid-derived suppressor cell.

• Factors related to the process of neoantigen production and presentation are discussed, such as TMB, MSI-H/dMMR, specific gene alternation, MHC molecules and T-cell receptor.

• Approaches that may soon contribute to a multiple biomarker strategy are summarized.

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

This paper was not funded.