PD-L1-Expressing Cancer-Associated Fibroblasts Have the Potential of a Biomarker for Immune Checkpoint Inhibitors

Programmed cell death 1(PD-1)/programmed cell death ligand 1(PD-L1)axis is well known as the system resulting in the inhibition of immune responses and promotion of self-tolerance. The clinical indications for immune checkpoint inhibitors( ICIs), including the targeting of PD-1/PD-L1 axis, are dramatically expanding. However, since ICIs have been found to be ineffective or resistant in some types of cancer, the development of more effective combination therapies or predictors and biomarkers of efficacy are expected. On the other hand, we have been focusing on the tumor microenvironment(TME)as a therapeutic target, and have been analyzing the function of cancer-associated fibroblasts(CAFs), which play a central role in TME. Recently, CAFs are known to induce tumors to an immunosuppressive state, suggesting that ICIs may not be effective in such a cancer microenvironment. In this review, we demonstrated the impact of PD-L1 positivity in cancer cells and CAFs by immunohistochemistry for resected specimens. In addition, we evaluated the potential of PD-L1-positve CAFs for therapeutic target and biomarker for ICIs.