Five latent factors underlie response to immunotherapy

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• dc.contributor.author Usset, Joseph
• dc.contributor.author Rosendahl Huber, Axel
• dc.contributor.author Andrianova, Maria A.
• dc.contributor.author Batlle Gómez, Eduard
• dc.contributor.author Carles, Joan
• dc.contributor.author Cuppen, Edwin
• dc.contributor.author Elez, Elena
• dc.contributor.author Felip, Enriqueta
• dc.contributor.author Gómez Rey, Marina
• dc.contributor.author Lo Giacco, Deborah
• dc.contributor.author Martínez Jiménez, Francisco
• dc.contributor.author Muñoz Couselo, Eva
• dc.contributor.author Siu, Lillian L.
• dc.contributor.author Tabernero Cartula, Josep
• dc.contributor.author Vivancos Prellezo, Ana
• dc.contributor.author Muiños, Ferran
• dc.contributor.author Gonzalez-Perez, Abel
• dc.contributor.author López Bigas, Núria
• dc.date.accessioned 2024-11-13T07:08:23Z
• dc.date.available 2024-11-13T07:08:23Z
• dc.date.issued 2024
• dc.description.abstract Only 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.
• dc.description.sponsorship We wish to acknowledge the contribution of patients, families and biomedical researchers who shared, processed and sequenced the data used in the study. This publication and the underlying study have been made possible partly based on the data that HMF has made available. We also acknowledge the use of data from the INSPIRE clinical trial (NCT02644369) and data obtained from patients presented at the VHIO. N.L.-B. acknowledges funding from the European Research Council (ERC; consolidator grant 682398). This project has received funding from the European Union’s Horizon program HORIZON-HLTH-2021-CARE-05-02 for the project CGI-Clinics under grant agreement no. 101057509. E.B. receives support from Generalitat de Catalunya (2021 SGR 001278) and ERC Advanced Grant 884623. The Institute for Research in Biomedicine Barcelona is a recipient of a Severo Ochoa Centre of Excellence Award from the Spanish Ministry of Economy and Competitiveness (MINECO; Government of Spain) and an Excellence Institutional grant by the Asociacion Española contra el Cancer and is supported by CERCA (Generalitat de Catalunya).
• dc.format.mimetype application/pdf
• dc.identifier.citation Usset 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/s41588-024-01899-0
• dc.identifier.doi http://dx.doi.org/10.1038/s41588-024-01899-0
• dc.identifier.issn 1061-4036
• dc.identifier.uri http://hdl.handle.net/10230/68509
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Nat Genet. 2024 Oct;56(10):2112-20
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/682398
• dc.relation.projectID info:eu-repo/grantAgreement/EC/HE/101057509
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/884623
• dc.rights © 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/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
• dc.subject.keyword Cancer therapy
• dc.title Five latent factors underlie response to immunotherapy
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion