Drug response to PD-1/PD-L1 blockade: based on biomarkers

Abstract

In recent years, immunotherapies targeting programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) have provided great hopes for patients with cancer. A successful anti-PD-1/PD-L1 therapy includes not only the elimination of immunosuppressive tumor cells but also the rejuvenation of exhausted T cells. Nevertheless, the efficacy of therapy is still low, so that biomarker-driven therapy has attracted more and more attention to identify patients who are likely to benefit from therapy and to reduce unnecessary disease progression. While many studies have focused on characteristics of tumor biopsies, biomarkers linked to T cell exhaustion and rejuvenation have just become new hot spots in drug response studies. However, no biomarker is perfect in drug response prediction currently, so there is an urgent need for other biomarkers to compensate for the deficiency. In this review, we summarize some approved and candidate biomarkers predictive of drug response before and during PD-1/PD-L1 blockade, including those characterizing responsive or suppressive tumor cells and those evaluating the T cell rejuvenation. Overall, we set up a comprehensive network of biomarkers of tumor characteristics and T cell rejuvenation, predicting drug response before and during anti-PD-1/PD-L1 therapies.

Keywords:

• PD-1
• PD-L1
• biomarker
• network
• tumor
• T cell rejuvenation

Acknowledgments

This review was supported by the National Natural Science Foundation of China (grants 81502353 and 61431019) and Beijing Obstetrics and Gynecology Hospital, Capital Medical University (FCYY201713). We would also like to show our gratitude to the “anonymous” reviewers for their insights that greatly improved the manuscript.

Author contributions

Qi Chen and Wentao Yue conceptualized, drafted, and revised the manuscript. Tianhe Li revised the manuscript. All authors contributed toward data analysis, drafting and revising the paper and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.