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Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
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.
Soluble PD-L1 shows no association to relapse and overall survival in early stage non-small cell lung cancer (NSCLC).
Lung Cancer. 2024; 196: 107955
Doi: 10.1016/j.lungcan.2024.107955
Web of Science
PubMed
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- Co-authors Med Uni Graz
- Kargl Julia
- Lindenmann Jörg
- Mykoliuk Iurii
- Raftopoulou Sofia
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- 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. 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. 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. 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.
- Find related publications in this database (Keywords)
- NSCLC
- sPD-L1
- Tumor immune microenvironment
- Biomarker
- Relapse prediction