{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["14(11)"],"submitter":["Gwin ME"],"pubmed_abstract":["<h4>Background</h4>In non-small cell lung cancer (NSCLC), programmed death-ligand 1 (PD-L1) expression has moderate ability to predict immune checkpoint inhibitor (ICI) benefit. In clinical practice, PD-L1, a cell surface protein, cannot be characterized in currently available blood-based tests such as circulating tumor DNA assays. To understand the biologic effects of PD-L1 more fully and evaluate whether blood-based tests could provide insight into its expression, we determined the association between PD-L1 expression and systemic immune parameters.<h4>Methods</h4>We collected pre- and post-treatment (6-week) peripheral blood samples in patients with NSCLC treated with ICI. Using multiplex panels and cytometry by time of flight (CyTOF), we analyzed specimens for baseline and post-treatment changes in cytokines, autoantibodies, and immune cell populations. We determined the association between case characteristics, immune parameters, and tumor PD-L1 expression (categorized as <1%, 1-49%, and ≥50%) using Chi-square, one-way analysis of variance (ANOVA), and Kruskal-Wallis tests, accounting for multiple comparisons.<h4>Results</h4>A total of 119 patients were included in the analysis, of whom 41 (34%) had PD-L1 expression <1%; 44 (37%), 1-49%; and 34 (29%), ≥50%. PD-L1 expression was not associated with any demographic, tumor, or treatment characteristics. Among 39 cytokines evaluated, baseline levels of macrophage migration inhibitory factor (MIF) were significantly greater in high PD-L1 positive cases. Among 124 autoantibodies included in the analysis, three (anti-aggrecan, -proteoglycan, and -nucleosome) demonstrated significantly greater post-ICI treatment increases in cases with higher PD-L1 expression. In PD-L1 positive cases, baseline abundance of natural killer T (NKT) cells (P=0.001) and activated monocytes (P=0.04) were significantly lower, while post-treatment increases in mature natural killer (NK) cells were significantly greater (P=0.006).<h4>Conclusions</h4>NSCLC PD-L1 expression is associated with few systemic immune parameters, suggesting that effects on anti-tumor immunity may occur predominantly in the tumor microenvironment and that blood-based assays are unlikely to provide meaningful surrogates of this biomarker."],"journal":["Translational lung cancer research"],"pagination":["4962-4972"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12683405"],"repository":["biostudies-literature"],"pubmed_title":["Association of PD-L1 expression with systemic immune parameters in non-small cell lung cancer."],"pmcid":["PMC12683405"],"pubmed_authors":["Liu J","Xie Y","Gwin ME","Yang DM","Dowell JE","Gerber DE","Rashdan S","Mu-Mosley H","Park JY","von Itzstein MS","Fattah FJ","Bhalla S","SoRelle JA"],"additional_accession":[]},"is_claimable":false,"name":"Association of PD-L1 expression with systemic immune parameters in non-small cell lung cancer.","description":"<h4>Background</h4>In non-small cell lung cancer (NSCLC), programmed death-ligand 1 (PD-L1) expression has moderate ability to predict immune checkpoint inhibitor (ICI) benefit. In clinical practice, PD-L1, a cell surface protein, cannot be characterized in currently available blood-based tests such as circulating tumor DNA assays. To understand the biologic effects of PD-L1 more fully and evaluate whether blood-based tests could provide insight into its expression, we determined the association between PD-L1 expression and systemic immune parameters.<h4>Methods</h4>We collected pre- and post-treatment (6-week) peripheral blood samples in patients with NSCLC treated with ICI. Using multiplex panels and cytometry by time of flight (CyTOF), we analyzed specimens for baseline and post-treatment changes in cytokines, autoantibodies, and immune cell populations. We determined the association between case characteristics, immune parameters, and tumor PD-L1 expression (categorized as <1%, 1-49%, and ≥50%) using Chi-square, one-way analysis of variance (ANOVA), and Kruskal-Wallis tests, accounting for multiple comparisons.<h4>Results</h4>A total of 119 patients were included in the analysis, of whom 41 (34%) had PD-L1 expression <1%; 44 (37%), 1-49%; and 34 (29%), ≥50%. PD-L1 expression was not associated with any demographic, tumor, or treatment characteristics. Among 39 cytokines evaluated, baseline levels of macrophage migration inhibitory factor (MIF) were significantly greater in high PD-L1 positive cases. Among 124 autoantibodies included in the analysis, three (anti-aggrecan, -proteoglycan, and -nucleosome) demonstrated significantly greater post-ICI treatment increases in cases with higher PD-L1 expression. In PD-L1 positive cases, baseline abundance of natural killer T (NKT) cells (P=0.001) and activated monocytes (P=0.04) were significantly lower, while post-treatment increases in mature natural killer (NK) cells were significantly greater (P=0.006).<h4>Conclusions</h4>NSCLC PD-L1 expression is associated with few systemic immune parameters, suggesting that effects on anti-tumor immunity may occur predominantly in the tumor microenvironment and that blood-based assays are unlikely to provide meaningful surrogates of this biomarker.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-06-05T23:50:13.025Z","creation":"2026-05-23T03:13:41.309Z"},"accession":"S-EPMC12683405","cross_references":{"pubmed":["41367556"],"doi":["10.21037/tlcr-2025-414"]}}