Journal article
Multicellular immune ecotypes within solid tumors predict real-world therapeutic benefits with immune checkpoint inhibitors
Nature communications, Vol.16(1), 9968
11/13/2025
DOI: 10.1038/s41467-025-65016-3
PMCID: PMC12615696
PMID: 41233329
Abstract
Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, yet predicting patient response remains a major challenge. Carcinoma ecotypes, which capture the cancer-immune interactions, show promise as prognostic biomarkers but remain untested in real-world settings. We compile and analyze the ORIEN Avatar ICI cohort of 1610 patients with matched gene expression data from a broader dataset of 14,997 individuals. Using EcoTyper-based immunophenotyping, we define ecotypes and assess their prognostic value across cancers, with a focused analysis in melanoma. Distinct cell states and ecotypes are consistently associated with survival outcomes across cancer types. We further develop a melanoma-specific ICI predictive model and validate it using data from the phase III ECOG-ACRIN E1609 trial as well as in external harmonized melanoma datasets. Together, these findings establish an ecotype-based framework and provide real-world evidence for their translational utility as clinically actionable biomarkers with prognostic and predictive value to guide ICI therapy.
Details
- Title: Subtitle
- Multicellular immune ecotypes within solid tumors predict real-world therapeutic benefits with immune checkpoint inhibitors
- Creators
- Xuefeng Wang - Moffitt Cancer CenterTingyi Li - Moffitt Cancer CenterIslam Eljilany - Moffitt Cancer CenterAlex Soupir - Moffitt Cancer CenterMichael Radmacher - Aster Insights, Hudson, FL, USAPhaedra Agius - Aster Insights, Hudson, FL, USAVineeth Sukrithan - The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research InstituteAakrosh Ratan - University of VirginiaMartin McCarter - University of Colorado DenverBodour Salhia - University of Southern CaliforniaHoward Colman - University of UtahAbdul R Naqash - University of Oklahoma Health Sciences CenterIgor Puzanov - Roswell Park Comprehensive Cancer CenterSusanne Arnold - Markey Cancer CenterJulian A Marin-Acevedo - Indiana University Melvin and Bren Simon Comprehensive Cancer CenterShridar Ganesan - Rutgers, The State University of New JerseyMichelle Churchman - Aster Insights, Hudson, FL, USAPatrick Hwu - Moffitt Cancer CenterPaulo C Rodriguez - Moffitt Cancer CenterWilliam S Dalton - Aster Insights, Hudson, FL, USAGeorge J Weiner - University of IowaAhmad A Tarhini - Moffitt Cancer Center
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.16(1), 9968
- DOI
- 10.1038/s41467-025-65016-3
- PMID
- 41233329
- PMCID
- PMC12615696
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Publisher
- Springer Nature
- Grant note
- R01DE030493 / U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research (NIDCR)
- Language
- English
- Date published
- 11/13/2025
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Pharmaceutical Sciences and Experimental Therapeutics; Internal Medicine
- Record Identifier
- 9985027362902771
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