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Soluble PD-L1 shows no association to relapse and overall survival in early stage non-small cell lung cancer (NSCLC).

Authors :
Mildner FO
Sykora MM
Hackl H
Amann A
Zelger B
Sprung S
Buch ML
Nocera F
Moser P
Maier H
Augustin F
Manzl C
Kocher F
Pircher A
Lindenmann J
Mykoliuk I
Raftopoulou S
Kargl J
Wolf D
Sopper S
Gamerith G
Source :
Lung cancer (Amsterdam, Netherlands) [Lung Cancer] 2024 Oct; Vol. 196, pp. 107955. Date of Electronic Publication: 2024 Sep 16.
Publication Year :
2024

Abstract

Background: Cancer immune evasion is critical in non-small cell lung cancer (NSCLC) and has been targeted by immunotherapy. High soluble (s)PD-L1 is associated with reduced survival and treatment failure in advanced stages. Here we evaluated the effects of sPD-L1 on T cells, relapse free survival, and overall survival in early stage NSCLC.<br />Methods: In vitro T cell stimulation was performed in the presence of sPD-L1 to evaluate its immunomodulatory activity. Data from The Cancer Genome Atlas (TCGA) were investigated for PD-L1 splice variants and enzymes involved in proteolytic cleavage (i.e. ADAM10). Plasma from 74 NSCLC (stage IA-IIIB), as well as an additional 73 (control cohort) patients was collected prior to curative surgery. Thereafter sPD-L1 levels from an immunosorbent assay were correlated with patient outcome.<br />Results: In vitro sPD-L1 inhibited IFN-γ production and proliferation of T cells and induced a terminal effector CD4 T cell subtype expressing CD27. Data from the TCGA demonstrated that elevated mRNA levels of ADAM10 is a negative predictor of outcome in NSCLC patients. To investigate the clinical relevance of these in vitro and TCGA findings, we quantified sPD-L1 in the plasma of early-stage NSCLC patients. In the first cohort we found significantly higher sPD-L1 levels in relapsing NSCLC patients, with a multivariate analysis revealing high sPD-L1 (>1000 pg/mL) as an independent predictor of survival. However, these findings could not be validated in two independent control cohorts.<br />Discussion: Although in vitro and TCGA data support the suppressive effect of sPD-L1 we were unable to translate this in our clinical setting. These results may be due to the small patient number and their heterogeneity as well as the lack of a standardized sPD-L1 ELISA. Our inconclusive results regarding the value of sPD-L1 in early stage NSCLC warrant assay validation and further investigation in larger (neo-)adjuvant trials.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Details

Language :
English
ISSN :
1872-8332
Volume :
196
Database :
MEDLINE
Journal :
Lung cancer (Amsterdam, Netherlands)
Publication Type :
Academic Journal
Accession number :
39306924
Full Text :
https://doi.org/10.1016/j.lungcan.2024.107955