Five latent factors underlie response to immunotherapy
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.
Authors
- Lillian L. Siu (ORCID: https://orcid.org/0000-0002-3500-0540)
- Joan Carles (ORCID: https://orcid.org/0000-0002-9983-5934)
- Josep M. Tabernero (ORCID: https://orcid.org/0000-0002-2495-8139)
- Ferran Muiños (ORCID: https://orcid.org/0000-0002-4651-4168)
- Deborah Lo Giacco
- Marina Gómez-Rey (ORCID: https://orcid.org/0000-0002-9636-3281)
- Núria López-Bigas (ORCID: https://orcid.org/0000-0003-4925-8988)
- Eva Muñoz‐Couselo (ORCID: https://orcid.org/0000-0001-7556-7608)
- Ana P. Vivancos (ORCID: https://orcid.org/0000-0003-2888-6512)
- Edwin Cuppen (ORCID: https://orcid.org/0000-0002-0400-9542)
- Axel Rosendahl Huber (ORCID: https://orcid.org/0000-0003-4001-5605)
- Abel González-Pérez (ORCID: https://orcid.org/0000-0002-8582-4660)
- Eduard Batlle (ORCID: https://orcid.org/0000-0003-2422-0326)
- Joseph Usset (ORCID: https://orcid.org/0000-0002-5820-9881)
- Maria Andrianova
- Francisco Martínez-Jiménez (ORCID: https://orcid.org/0000-0001-7804-1134)
- Enriqueta Felip (ORCID: https://orcid.org/0000-0002-7620-0098)
- Elena Élez
Institutions
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Universitat Pompeu Fabra (ES)
- Instituto de Salud Carlos III (ES)
- Princess Margaret Cancer Centre (CA)
- University Medical Center Utrecht (NL)
- Institute for Research in Biomedicine (ES)
- Vall d'Hebron Hospital Universitari (ES)
- Hartwig Medical Foundation (NL)
- Centro de Investigación Biomédica en Red de Cáncer (ES)
- Vall d'Hebron Institute of Oncology (ES)
Publication Details
- Journal
- Nature Genetics
- Published
- 2024-09-12
- DOI
- https://doi.org/10.1038/s41588-024-01899-0
- Citations
- 29
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 8.19
Funders
- Institute for Research in Biomedicine
- Centres de Recerca de Catalunya
- European Commission
- Generalitat de Catalunya
- Ministerio de Economía y Competitividad