Usset, JosephRosendahl Huber, AxelAndrianova, Maria A.Batlle Gómez, EduardCarles, JoanCuppen, EdwinElez, ElenaFelip, EnriquetaGómez Rey, MarinaLo Giacco, DeborahMartínez Jiménez, FranciscoMuñoz Couselo, EvaSiu, Lillian L.Tabernero Cartula, JosepVivancos Prellezo, AnaMuiños, FerranGonzalez-Perez, AbelLópez Bigas, Núria2024-11-132024-11-132024Usset J, Rosendahl Huber A, Andrianova MA, Batlle E, Carles J, Cuppen E, et al. Five latent factors underlie response to immunotherapy. Nat Genet. 2024 Oct;56(10):2112-20. DOI: 10.1038/s41588-024-01899-01061-4036http://hdl.handle.net/10230/68509Only a subset of patients treated with immune checkpoint inhibitors (CPIs) respond to the treatment, and distinguishing responders from non-responders is a major challenge. Many proposed biomarkers of CPI response and survival probably represent alternative measurements of the same aspects of the tumor, its microenvironment or the host. Thus, we currently ignore how many truly independent biomarkers there are. With an unbiased analysis of genomics, transcriptomics and clinical data of a cohort of patients with metastatic tumors (n = 479), we discovered five orthogonal latent factors: tumor mutation burden, T cell effective infiltration, transforming growth factor-beta activity in the microenvironment, prior treatment and tumor proliferative potential. Their association with CPI response and survival was observed across all tumor types and validated across six independent cohorts (n = 1,491). These five latent factors constitute a frame of reference to organize current and future knowledge on biomarkers of CPI response and survival.application/pdfeng© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41588-024-01899-0Cancer therapyinfo:eu-repo/semantics/openAccess