PD-L1 expression in systemic immune cell populations as a potential predictive biomarker of responses to PD-L1/PD-1 blockade therapy in lung cancer

Bocanegra Gondán, Ana IsabelFernández Hinojal, GonzaloZuazo Ibarra, MirenArasanz Esteban, HugoGarcía Granda, María JesúsHernández, CarlosIbañez Vea, MaríaHernandez Marin, BertaMartínez Aguillo, MaiteLecumberri, María JoséFernández de Lascoiti, ÁngelaTeijeira, LucíaMorilla Ruiz, IdoiaVera García, RuthEscors Murugarren, DavidKochan, Grazyna2022-08-082022-08-082019Bocanegra, A.; Fernandez-Hinojal, G.; Zuazo-Ibarra, M.; Arasanz, H.; Garcia-Granda, M.J.; Hernandez, C.; Ibañez, M.; Hernandez-Marin, B.; Martinez-Aguillo, M.; Lecumberri, M.J.; Fernandez de Lascoiti, A., Teijeira, L., Morilla, I., Vera, R.; Escors, D.; Kochan, G.. (2019). PD-L1 Expression in Systemic Immune Cell Populations as a Potential Predictive Biomarker of Responses to PD-L1/PD-1 Blockade Therapy in Lung Cancer. International Journal of Molecular Sciences. 20,7.1661-659610.3390/ijms20071631https://academica-e.unavarra.es/handle/2454/43707PD-L1 tumor expression is a widely used biomarker for patient stratification in PD-L1/PD-1 blockade anticancer therapies, particularly for lung cancer. However, the reliability of this marker is still under debate. Moreover, PD-L1 is widely expressed by many immune cell types, and little is known on the relevance of systemic PD-L1+ cells for responses to immune checkpoint blockade. We present two clinical cases of patients with non-small cell lung cancer (NSCLC) and PD-L1-negative tumors treated with atezolizumab that showed either objective responses or progression. These patients showed major differences in the distribution of PD-L1 expression within systemic immune cells. Based on these results, an exploratory study was carried out with 32 cases of NSCLC patients undergoing PD-L1/PD-1 blockade therapies, to compare PD-L1 expression profiles and their relationships with clinical outcomes. Significant differences in the percentage of PD-L1+ CD11b+ myeloid cell populations were found between objective responders and non-responders. Patients with percentages of PD-L1+ CD11b+ cells above 30% before the start of immunotherapy showed response rates of 50%, and 70% when combined with memory CD4 T cell profiling. These findings indicate that quantification of systemic PD-L1+ myeloid cell subsets could provide a simple biomarker for patient stratification, even if biopsies are scored as PD-L1 nullapplication/pdfeng© 2022 by the authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) licensePD-L1BiomarkerLung cancerImmunotherapyImmune checkpoint blockadePD-L1 expression in systemic immune cell populations as a potential predictive biomarker of responses to PD-L1/PD-1 blockade therapy in lung cancerinfo:eu-repo/semantics/article2022-08-08info:eu-repo/semantics/openAccess