Journal
MOLECULAR CANCER
Volume 17, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s12943-018-0864-3
Keywords
PD-1/PD-L1 inhibitors; Predictive biomarkers; Tumor mutational burden; Microsatellite instability; Gut microbiota; Peripheral biomarker
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Funding
- National Natural Science Foundation of China [81572608, 81172422]
- Wuhan Science and Technology Bureau [2017060201010170]
- National High Technology Research and Development Program of China [2015AA020301]
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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.
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