Unleashing the immune system: PD-1 and PD-Ls in the pre-treatment tumor microenvironment and correlation with response to PD-1/PD-L1 blockade

Abstract

Focal tumor cell PD-L1 expression adjacent to TIL can be used as a surrogate marker of an ongoing antitumor host response, which may be unleashed by PD-1 blockade. Tumor cell PD-L1 expression is superior to TIL PD-1 expression and the presence of TIL alone, when predicting response to anti-PD-1 therapy.

Keywords: CRPC, castration-resistant prostate cancer; FFPE, formalin-fixed paraffin-embedded; NSCLC, non-small cell lung carcinoma; PD-1; PD-1, programmed death 1; PD-L1; PD-L1, programmed death-ligand 1; PD-L2; PD-L2, programmed death-ligand 2; RCC, renal cell carcinoma; TIL, tumor-infiltrating lymphocytes; cancer immunotherapy; tumor microenvironment.

Figures

Figure 1

Tumor PD-L1 is the strongest single predictor of response to anti-PD-1. When analyzing either the highest scoring sample among multiple biopsies from individual patients or the specimen obtained closest to therapy, tumor cell PD-L1 expression correlated with objective response to anti-PD-1 therapy. This association was stronger than the borderline association with PD-1 expression. Simply the presence of intratumoral immune cell infiltrates did not correlate with response. Additional features examined that did not predict response to anti-PD-1 in this limited cohort included PD-L2 expression by tumor or immune cells, CD4+:CD8+ ratio, CD20+ B−cells, or the presence of lymphoid aggregates or tumor necrosis (data not shown).