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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.

SUBMITTER: Gavrielatou N 

PROVIDER: S-EPMC8776595 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Publications

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

Gavrielatou Niki N   Liu Yuting Y   Vathiotis Ioannis I   Zugazagoitia Jon J   Aung Thazin Nwe TN   Shafi Saba S   Fernandez Aileen A   Schalper Kurt K   Psyrri Amanda A   Rimm David L DL  

Clinical cancer research : an official journal of the American Association for Cancer Research 20211022 2


<h4>Purpose</h4>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).<h4>Experimental design</h4>Pretreatment biopsies from a retrospective cohort of 154 immunotherapy-treated patients with advanced  ...[more]

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