| Title: |
Interrogating the immune landscape of microsatellite stable RAS-mutated colon cancer |
| Authors: |
Dienstmann, Rodrigo; Garcia-galea, Eduardo; O'farrell, Alice; Kinsella, Zak; Meylan, Maxime; Petitprez, Florent; Arijs, Ingrid; Venken, Tom; Ps, Hari; Larkeryd, Adrian; Miller, Ian; Selves, Janick; Meindl-beinker, Nadja; Ruiz-pace, Fiorella; Elez, Elena; Comas-navarro, Raquel; Lincoln, Frank; Fey, Dirk; Nyamundanda, Gift; Nolan, Aoife; Lewin, Joern; Perez-lopez, Raquel; Briody, Jonathan; Bennett, Kathleen; Kolch, Walter; Matallanas, David; Kel, Alexander; Arenas, Enrique; Arribas, Joaquin; Ghesquiere, Bart; Tabernero, Josep; Meilleroux, Julie; Mcnamara, Deborah; Mcdermott, Ray; Lim, Marvin; O'reilly, Mary; Bird, Brian; Stack, Lisa; Moloney, Lucia; Morris, Patrick; Egan, Keith; Milewski, Maciej; Scheuer, Lars; Behringer, Joachim; Bolz, Georg; Salazar, Ramon; Santos, Cristina; Ruiz, Andrea; Casey, Orla; Murphy, Verena; Ebert, Matthias; Trusolino, Livio; Lambrechts, Diether; Sadanandam, Anguraj; Sautes-fridman, Catherine; Prehn, Jochen; Nuciforo, Paolo; Fieschi, Jacques; Monville, Florence; O'connor, Darran; Fridman, Wolf; Byrne, Annette |
| Source: |
ISSN:1574-7891 ; ISSN:1878-0261 ; Molecular Oncology. |
| Publisher Information: |
Wiley |
| Publication Year: |
2026 |
| Subject Terms: |
Science & Technology; Life Sciences & Biomedicine; Oncology; colorectal cancer; immuno-markers; immunoscore; microsatellite stable; RAS mutation; tumor-infiltrating lymphocytes; immuno‐markers; tumor‐infiltrating lymphocytes; 1112 Oncology and Carcinogenesis; Oncology & Carcinogenesis; 3211 Oncology and carcinogenesis |
| Description: |
To explore the immune microenvironment of RAS-mutated (RASmt) microsatellite stable (MSS) colon cancer (CC), we retrospectively performed whole exome sequencing, RNA sequencing, and robust digital pathology analyses and studied immune markers in a cohort of 161 patients treated with standard-of-care therapies with early stage disease (both fresh frozen and formalin-fixed paraffin-embedded [FFPE] samples) or 121 patients with metastatic setting (primary tumor FFPE samples). Only a small proportion of cases exhibited a highly infiltrated immune microenvironment, with a strong association between Immunoscore® (IS)-high (13% of the samples) and Tumor Lymphocytes Infiltrating Score (TuLIS)-high scores (25% of the samples). Immunoscore Immune-Checkpoint (ISIC)-high tumors (52% of the samples) shared a similar microenvironment composition to IS-high and TuLIS-like high tumors and displayed higher mutational burdens than ISIC-low tumors. In conclusion, a substantial proportion of MSS RASmt CCs exhibit high ISIC scores, meriting evaluation in prospective trials of immunotherapy-based combination regimens. ; sponsorship: This project was funded by the European Union Studies Association program under grant agreement No 754923 ('COLOSSUS'). ATB acknowledges funding from Research Ireland (20/FFP-P/8884). This work was also conducted with funding from the Italian Ministry of Health, Ricerca Corrente 2025, to the Candiolo Cancer Institute FPO IRCCS; AIRC, Associazione Italiana per la Ricerca sul Cancro, Investigator Grant 30315 (to L.T.); Fondazione Piemontese per la Ricerca sul Cancro-ONLUS, 5x1000 Ministero della Salute 2022, grant CARESS (to L.T.); Italian Ministry of University and Research, National Recovery and Resilience Plan (PNRR), project PNC0000001 (to L.T.). (European Union Studies Association) ; status: Published online |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://lirias.kuleuven.be/handle/20.500.12942/782808; https://pubmed.ncbi.nlm.nih.gov/41733106 |
| DOI: |
10.1002/1878-0261.70225 |
| Availability: |
https://lirias.kuleuven.be/handle/20.500.12942/782808; https://hdl.handle.net/20.500.12942/782808; https://lirias.kuleuven.be/retrieve/6fc20221-94e1-44ce-bd15-02caa4c8a36d; https://doi.org/10.1002/1878-0261.70225; https://pubmed.ncbi.nlm.nih.gov/41733106 |
| Rights: |
info:eu-repo/semantics/openAccess ; public ; https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.85D0B0E4 |
| Database: |
BASE |