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

Abstract

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 current 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: Pretreatment biopsies from a retrospective cohort of 154 immunotherapy-treated patients with advanced NSCLC were analyzed. 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 tumor proportion score 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: On the basis of 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 patients with NSCLC receiving treatment with immune checkpoint inhibitors.

Multiplexed imaging of tumor immune microenvironmental markers in locally advanced or metastatic non‐small‐cell lung cancer characterizes the features of response to PD‐1 blockade plus chemotherapy

“…CD68 is the classic tumor-associated macrophage marker, a double-edged sword in antitumor immunity. Previous studies revealed CD68+ macrophages were the predominant immune cell type expressing PD-L1 [38,39].…”

“…CD68 is the classic tumor‐associated macrophage marker, a double‐edged sword in antitumor immunity. Previous studies revealed CD68+ macrophages were the predominant immune cell type expressing PD‐L1 [ 38 , 39 ]. A high level of PD‐L1 in macrophages was significantly correlated with a high level of PD‐L1 expression in tumor cells and CD8+ T cells infiltration, indicating an inflamed TME phenotype [ 38 , 39 ].…”

“…Previous studies revealed CD68+ macrophages were the predominant immune cell type expressing PD‐L1 [ 38 , 39 ]. A high level of PD‐L1 in macrophages was significantly correlated with a high level of PD‐L1 expression in tumor cells and CD8+ T cells infiltration, indicating an inflamed TME phenotype [ 38 , 39 ]. Positive PD‐L1 expression in CD68+ macrophages was associated with significantly better treatment outcomes in patients treated with anti‐PD‐1/PD‐L1 monotherapy [ 39 , 40 ].…”

Characteristics of the immune microenvironment and their clinical significance in non-small cell lung cancer patients with ALK-rearranged mutation

“…Spatial profiling technologies are powerful tool to analyze immune cell typing, immune activation and therapeutic options ( 33 , 34 ). Likewise, co-location of immuno-biomarkers can be used as prognostic indicators ( 35 ).…”

PD‐1/PD‐L1 co‐location: A novel biomarker for immunotherapy response in non‐small cell lung cancer

“…In a study recently published in Clinical Cancer Research , titled “Association of PD‐1/PD‐L1 Co‐location with Immunotherapy Outcomes in Non‐Small Cell Lung Cancer,” Gavrielatou et al 11 assessed the co‐location of PD‐1 and PD‐L1 on a retrospective cohort of 154 advanced NSCLC patients treated with immune checkpoint inhibitor. Expression of PD‐1 and PD‐L1 was detected by multiplex quantitative immunofluorescence.…”