2026-04-13T14:24:45Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/122342025-10-04T05:19:40Zcom_2072_378070com_2072_378040col_2072_378092

00925njm 22002777a 4500 dc Usset, Joseph author Huber, Axel Rosendahl author Andrianova, Maria A. author Batlle, Eduard author Lo Giacco, Deborah author Cuppen, Edwin author Elez, Elena author Gómez-Rey, Marina author Martínez-Jiménez, Francisco author MUÑOZ COUSELO, EVA author Tabernero, Josep author Vivancos, Ana author Carles, Joan author FELIP, ENRIQUETA author 2024-11-19T08:43:51Z 2024-11-19T08:43:51Z 2024-10 Response; Immunotherapy Respuesta; Inmunoterapia Resposta; Immunoteràpia 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. 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). Marcadors bioquímics Càncer - Immunoteràpia Medicaments antineoplàstics - Ús terapèutic DISEASES::Neoplasms Other subheadings::Other subheadings::Other subheadings::/drug therapy ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy CHEMICALS AND DRUGS::Biological Factors::Biomarkers::Biomarkers, Tumor CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents::Antineoplastic Agents, Immunological ENFERMEDADES::neoplasias Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapia biológica::inmunomodulación::inmunoterapia COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores::marcadores tumorales COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos::inmunoterapia antineoplásica Five latent factors underlie response to immunotherapy