ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Transcriptomic Signatures of MSI-High Metastatic Colorectal Cancer Predict Efficacy of Immune Checkpoint Inhibitors.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Trial
- Inflammation and mutational burden differentially associated with nivolumab or ipilimumab combination efficacy in colorectal cancer.Nature communications · 2025Trial
- Review
- A Lightweight Workflow for Targeted Long-Read Transcriptomic Profiling Using Oxford Nanopore Sequencing.Methods and protocols · 2026Article
- Checkpoint inhibitors in microsatellite instability-high metastatic colorectal cancer: treatment strategies, specificities, and care management questions.ESMO gastrointestinal oncology · 2026Review
- Impact of germline MMR gene variants on immune checkpoint inhibitors response in patients with MSI-H/dMMR digestive cancers: a retrospective cohort analysis.Hereditary cancer in clinical practice · 2026Article
- Mucinous histology and resistance to immune checkpoint blockade in patients with microsatellite instability-high metastatic colorectal cancer.The oncologist · 2026Article
- Decoding Immunotherapy Response in Colorectal Cancer: Translational Insights Beyond MSI.Cancers · 2026Review
- Pan-cancer analysis of TRPV1: a novel immune infiltration-related biomarker for tumor prognosis and immunotherapy response prediction.BMC cancer · 2026Article
- Emerging nano-immunotherapeutic strategies achieve metastatic colorectal cancer precision therapy.Journal of nanobiotechnology · 2026Review
- PET Imaging of System A Amino Acid Transport Detects Early Response to Immune Checkpoint Inhibitor Therapy in a Syngeneic Mouse Model.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2025Article
- Neoadjuvant immunotherapy for dMMR/MSI-H locally advanced rectal cancer patients: demystifying the 100% clinical complete response paradigm.The oncologist · 2025Article
- Therapeutic targeting of mismatch repair-deficient cancers.Nature reviews. Clinical oncology · 2025Review
- Prognostic and therapeutic value of a 23-gene risk score tailored to the molecular characteristics of mucinous colorectal cancer.British journal of cancer · 2025Article
- Spatial Heterogeneity, Stromal Phenotypes, and Therapeutic Vulnerabilities in Colorectal Cancer Peritoneal Metastasis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Epidemiology, pathogenesis, biology and evolving management of MSI-H/dMMR cancers.Nature reviews. Clinical oncology · 2025Review
- Spatially Resolved, Multiregion Proteomics for Prediction of Immunotherapy Outcome in Deficient Mismatch Repair Metastatic Colorectal Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Sex and outcomes of patients with microsatellite instability-high andJournal for immunotherapy of cancer · 2025Article
- Gastrointestinal tumor personalized immunotherapy: an integrated analysis from molecular genetics to imaging biomarkers.Therapeutic advances in gastroenterology · 2025Review
- Predictors of response to immunotherapy in colorectal cancer.The oncologist · 2024Review
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22 authors.
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Abstract
purposeMicrosatellite instability (MSI) is currently the only predictive biomarker of efficacy of immune checkpoint inhibitors (ICI) in metastatic colorectal cancers (mCRC). However, 10% to 40% of patients with MSI mCRC will experience a primary resistance to ICI. EXPERIMENTAL
designIn two cohorts of patients with MSI mCRC treated with ICI (exploratory, N = 103; validation, N = 35), 3' RNA sequencing was performed from primary tumors. Previously described single-cell transcriptomic signatures of tumor microenvironment (TME) were analyzed.
resultsIn the exploratory cohort, the unsupervised clustering allowed the identification of three clusters of tumors with distinct transcriptional profiles: cluster A ("stromalHIGH-proliferationLOW"), cluster B ("stromalHIGH-proliferationMED"), and cluster C ("stromalLOW-proliferationHIGH"), with an enrichment of patients progressing at first disease assessment under ICI in cluster A (30% vs. 12% in cluster B and 8.1% in cluster C; P = 0.074). Progression-free survival (PFS) was also significantly shorter in patients belonging to cluster A, compared with clusters B or C (P < 0.001) with 2-year PFS rates of 33.5%, 80.5%, and 78.3%, respectively. In multivariate analysis, PFS was still significantly longer in patients belonging to cluster B [HR, 0.19; 95% confidence interval (CI), 0.08-0.45; P < 0.001] and cluster C (HR, 0.25; 95% CI, 0.10-0.59; P = 0.02), compared with patients belonging to cluster A. The association of this clustering with PFS under ICI was confirmed in the validation cohort. PFS related to non-ICI-based regimens was not significantly different according to cluster.
conclusionsThis unsupervised transcriptomic classification identified three groups of MSI mCRCs with different compositions of TME cells and proliferative capacities of TME/tumor cells. The "stromalHIGH-proliferationLOW" cluster is associated with a poorer prognosis with ICI treatment.
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