Article Impact Level: HIGH Data Quality: STRONG Summary of Nature Genetics, 1–9. https://doi.org/10.1038/s41588-024-01899-0 Dr. Joseph Usset et al.
Points
- Researchers analyzed genomic, transcriptomic, and clinical data from 479 metastatic tumor patients to identify independent biomarkers predicting response to immune checkpoint inhibitors (CPIs).
- The study identified five independent factors associated with CPI response: tumor mutation burden (TMB), effective T cell infiltration, TGF-β activity in the tumor microenvironment, prior treatments, and tumor proliferative potential.
- The findings were validated using six independent cohorts, totaling 1,491 patients, confirming the associations of these five factors with CPI treatment response and overall survival.
- These five latent factors provide a comprehensive framework for organizing current and future biomarkers related to CPI response and patient survival.
- The model offers insights into distinct biological pathways and patient histories, guiding personalized therapeutic strategies to identify CPI responders better and improve patient outcomes.
Summary
Researchers extensively analyzed genomic, transcriptomic, and clinical data from a cohort of 479 patients with metastatic tumors to identify independent biomarkers predicting response to immune checkpoint inhibitors (CPIs). Recognizing that only a subset of patients respond to CPI therapy and that many proposed biomarkers might measure overlapping tumor characteristics, the study aimed to determine the minimal independent factors associated with treatment outcomes.
The analysis uncovered five orthogonal latent factors: tumor mutation burden (TMB), effective T cell infiltration, transforming growth factor-beta (TGF-β) activity in the tumor microenvironment, prior treatments received by patients, and tumor proliferative potential. These factors were independently associated with CPI response and survival across various tumor types. To validate these findings, the researchers examined six independent cohorts totaling 1,491 patients, confirming the associations of the five factors with treatment response and overall survival.
These five latent factors provide a foundational framework for organizing current and future biomarkers related to CPI response and survival. By highlighting distinct biological pathways and patient histories influencing treatment efficacy, this model enhances the ability to distinguish responders from non-responders. This framework may guide personalized therapeutic strategies and improve outcomes for patients undergoing CPI therapy.
Link to the article: https://www.nature.com/articles/s41588-024-01899-0
References Usset, J., Rosendahl Huber, A., Andrianova, M. A., Batlle, E., Carles, J., Cuppen, E., Elez, E., Felip, E., Gómez-Rey, M., Lo Giacco, D., Martinez-Jimenez, F., Muñoz-Couselo, E., Siu, L. L., Tabernero, J., Vivancos, A., Muiños, F., Gonzalez-Perez, A., & Lopez-Bigas, N. (2024). Five latent factors underlie response to immunotherapy. Nature Genetics, 1–9. https://doi.org/10.1038/s41588-024-01899-0
