Biomarkers for predicting efficacy of PD-1/PD-L1 inhibitors

Abstract

Abstract Programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) is a negative modulatory signaling pathway for activation of T cell. It is acknowledged that PD-1/PD-L1 axis plays a crucial role in the progression of tumor by altering status of immune surveillance. As one of the most promising immune therapy strategies, PD-1/PD-L1 inhibitor is a breakthrough for the therapy of some refractory tumors. However, response rate of PD-1/PD-L1 inhibitors in overall patients is unsatisfactory, which limits the application in clinical practice. Therefore, biomarkers which could effectively predict the efficacy of PD-1/PD-L1 inhibitors are crucial for patient selection. Biomarkers reflecting tumor immune microenvironment and tumor cell intrinsic features, such as PD-L1 expression, density of tumor infiltrating lymphocyte (TIL), tumor mutational burden, and mismatch-repair (MMR) deficiency, have been noticed to associate with treatment effect of anti-PD-1/anti-PD-L1 therapy. Furthermore, gut microbiota, circulating biomarkers, and patient previous history have been found as valuable predictors as well. Therefore establishing a comprehensive assessment framework involving multiple biomarkers would be meaningful to interrogate tumor immune landscape and select sensitive patients.

Keywords

• PD-1/PD-L1 inhibitors
• Predictive biomarkers
• Tumor mutational burden
• Microsatellite instability
• Gut microbiota
• Peripheral biomarker