Escors Murugarren, DavidBocanegra Gondán, Ana IsabelChocarro de Erauso, LuisaBlanco, EsterPiñeiro Hermida, SergioGarnica, MaiderFernández Rubio, LeticiaVera García, RuthArasanz Esteban, HugoKochan, Grazyna2023-04-192023-04-192022Escors, D., Bocanegra, A., Chocarro, L., Blanco, E., Piñeiro-Hermida, S., Garnica, M., Fernandez-Rubio, L., Vera, R., Arasanz, H., & Kochan, G. (2022). Systemic cd4 immunity and pd-l1/pd-1 blockade immunotherapy. International Journal of Molecular Sciences, 23(21), 13241. https://doi.org/10.3390/ijms2321132411661-659610.3390/ijms232113241https://academica-e.unavarra.es/handle/2454/45140PD-L1/PD-1 blockade immunotherapy has changed the therapeutic approaches for the treatment of many cancers. Nevertheless, the mechanisms underlying its efficacy or treatment failure are still unclear. Proficient systemic immunity seems to be a prerequisite for efficacy, as recently shown in patients and in mouse models. It is widely accepted that expansion of anti-tumor CD8 T cell populations is principally responsible for anti-tumor responses. In contrast, the role of CD4 T cells has been less studied. Here we review and discuss the evidence supporting the contribution of CD4 T cells to anti-tumor immunity, especially recent advances linking CD4 T cell subsets to efficacious PD-L1/PD-1 blockade immunotherapy. We also discuss the role of CD4 T cell memory subsets present in peripheral blood before the start of immunotherapies, and their utility as predictors of response.application/pdfeng© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.BiomarkerImmune checkpointT lymphocytesinfo:eu-repo/semantics/article2023-04-19info:eu-repo/semantics/openAccess