ArticleTranslational lung cancer research2025
Association of PD-L1 expression with systemic immune parameters in non-small cell lung cancer.
Article in Translational lung cancer research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: 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. Methods: 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. Results: 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). Conclusions: 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.
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