Association of PD-1/PD-L1 Co-location with Immunotherapy Outcomes in Non-Small Cell Lung Cancer.

Purpose: Programmed cell death protein 1(PD-1)/programmed death-ligand 1 (PD-L1) interaction suppresses local T cell responses and promotes peripheral tolerance. In the present study, we focus on PD-1/PD-L1 co-location as a surrogate for this interaction and assess its association with immunotherapy outcomes in patients with non-small cell lung cancer (NSCLC). Experimental Design: Pre-treatment biopsies from a retrospective cohort of 154 immunotherapy-treated patients with advanced NSCLC were analysed. Expression of PD-1 and PD-L1 was assessed by multiplexed quantitative immunofluorescence (QIF) and PD-1 expression in the same pixels as PD-L1 (called a co-location score) was measured using an algorithm to define overlapping expression areas. Co-location scores were correlated with immunotherapy outcomes and PD-L1 tumor proportion score. Results: PD-1/PD-L1 co-location score was associated with best overall response (p=0.0012), progression free survival (p=0.0341) and overall survival after immunotherapy (p=0.0249). The association was driven by patients receiving immune checkpoint inhibitors in the second or subsequent line of treatment. PD-L1 TPS by IHC was also correlated with best overall response and progression-free survival. PD-L1 measured within the tumor compartment by QIF did not show any significant association with either best overall response or overall survival. Finally, co-location score was not associated with PD-L1 expression by either method. Conclusions: Based on our findings, co-location score shows promise as a biomarker associated with outcome after immunotherapy. With further validation, it could have value as a predictive biomarker for the selection of NSCLC patients receiving treatment with immune checkpoint inhibitors.