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Interrogating the immune landscape of microsatellite stable RAS-mutated colon cancer: short report

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...

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Main Authors: Dienstmann, Rodrigo (Author) , García-Galea, Eduardo (Author) , O'Farrell, Alice (Author) , Kinsella, Zak (Author) , Meylan, Maxime (Author) , Petitprez, Florent (Author) , Arijs, Ingrid (Author) , Venken, Tom (Author) , Ps, Hari (Author) , Lärkeryd, Adrian (Author) , Miller, Ian (Author) , Selves, Janick (Author) , Meindl-Beinker, Nadja M. (Author) , Ruiz-Pace, Fiorella (Author) , Élez, Elena (Author) , Comas-Navarro, Raquel (Author) , Lincoln, Frank (Author) , Fey, Dirk (Author) , Nyamundanda, Gift (Author) , Nolan, Aoife (Author) , Lewin, Joern (Author) , Perez-Lopez, Raquel (Author) , Briody, Jonathan (Author) , Bennett, Kathleen (Author) , Kolch, Walter (Author) , Matallanas, David (Author) , Kel, Alexander (Author) , Arenas, Enrique (Author) , Arribas, Joaquín (Author) , Ghesquière, Bart (Author) , Tabernero, Josep (Author) , Meilleroux, Julie (Author) , McNamara, Deborah (Author) , McDermott, Ray (Author) , Lim, Marvin (Author) , O'Reilly, Mary (Author) , Bird, Brian (Author) , Stack, Lisa (Author) , Moloney, Lucia (Author) , Morris, Patrick (Author) , Egan, Keith (Author) , Milewski, Maciej (Author) , Scheuer, Lars (Author) , Behringer, Joachim (Author) , Bolz, Georg (Author) , Salazar, Ramon (Author) , Santos, Cristina (Author) , Ruiz, Andrea (Author) , Casey, Orla (Author) , Murphy, Verena (Author) , Ebert, Matthias (Author) , Trusolino, Livio (Author) , Lambrechts, Diether (Author) , Sadanandam, Anguraj (Author) , Sautès-Fridman, Catherine (Author) , Prehn, Jochen (Author) , Nuciforo, Paolo (Author) , Fieschi, Jacques (Author) , Monville, Florence (Author) , O'Connor, Darran (Author) , Fridman, Wolf (Author) , Byrne, Annette (Author)
Format: Article (Journal)
Language:English
Published: 2026
In: Molecular oncology
Year: 2026, Pages: 1-13
ISSN:1878-0261
DOI:10.1002/1878-0261.70225
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1002/1878-0261.70225
Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/1878-0261.70225
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Author Notes:Rodrigo Dienstmann, Eduardo García-Galea, Alice O'Farrell, Zak Kinsella, Maxime Meylan, Florent Petitprez, Ingrid Arijs, Tom Venken, Hari Ps, Adrian Lärkeryd, Ian Miller, Janick Selves, Nadja Meindl-Beinker, Fiorella Ruiz-Pace, Elena Élez, Raquel Comas-Navarro, Frank Lincoln, Dirk Fey, Gift Nyamundanda, Aoife Nolan, Joern Lewin, Raquel Perez-Lopez, Jonathan Briody, Kathleen Bennett, Walter Kolch, David Matallanas, Alexander Kel, Enrique Arenas, Joaquín Arribas, Bart Ghesquière, Josep Tabernero, Julie Meilleroux, Deborah McNamara, Ray McDermott, Marvin Lim, Mary O'Reilly, Brian Bird, Lisa Stack, Lucia Moloney, Patrick Morris, Keith Egan, Maciej Milewski, Lars Scheuer, Joachim Behringer, Georg Bolz, Ramon Salazar, Cristina Santos, Andrea Ruiz, Orla Casey, Verena Murphy, Matthias Ebert, Livio Trusolino, Diether Lambrechts, Anguraj Sadanandam, Catherine Sautès-Fridman, Jochen Prehn, Paolo Nuciforo, Jacques Fieschi, Florence Monville, Darran O'Connor, Wolf Fridman and Annette Byrne
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Summary: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.
Item Description:Erstmals veröffentlicht: 24. Februar 2026
Gesehen am 12.03.2026
Physical Description:Online Resource
ISSN:1878-0261
DOI:10.1002/1878-0261.70225

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