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Ninety-five percent of advanced bowel cancers ignore immunotherapy, and the only real signal so far came in patients without active liver secondaries. Trials keep enrolling by treatment line rather than by immune biology, which guarantees the responders are diluted away.
Le's original study set the boundary: 40 percent response in mismatch repair-deficient colorectal cancer, 0 of 18 in proficient disease, with 1,782 against 73 somatic mutations per tumour. Botensilimab, an Fc-enhanced anti-CTLA-4 antibody, with balstilimab gave the first credible microsatellite stable signal: 17 percent response and 61 percent disease control in 101 evaluable heavily pre-treated patients, with responses concentrated in those without active liver metastases.
The field has two measurable handles it does not use for enrolment. Galon's immune contexture showed in 2006 that the type, density and location of T cells in a colorectal tumour predicts outcome better than stage, and the consensus molecular subtypes separate the immune-infiltrated CMS1 and the mesenchymal, TGF-beta-driven CMS4 that excludes T cells. A trial that enrolled by Immunoscore band, CMS class and liver-metastasis status would test the combination in the population where the mechanism predicts it can work, rather than in whoever has exhausted chemotherapy.
The first credible response signal in microsatellite stable colorectal cancer, and the reason the field's attention has moved to Fc engineering and to excluding patients with active liver metastases, in whom responses are rare.
The paper that split colorectal cancer into two diseases for immunotherapy purposes, and the direct ancestor of the first tumour-agnostic drug approval two years later.
The CMS framework organises colorectal cancer biology and trial stratification; BRAF V600E tumours cluster in CMS1, and CMS4's poor prognosis and stromal signalling are targets of ongoing research.
This paper showed that the immune response to a cancer is part of its prognosis, not background noise, and it introduced the idea of the immune contexture that underlies both the Immunoscore and the biomarker work in immunotherapy.
Shares PD-1 blockade in tumors with mismatch-repair deficiency, Neoantigen, No one can predict who responds to immunotherapy, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR) and the tag colorectal-evidence.
Shares CTLA-4, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Ipilimumab, Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation and the tag colorectal-evidence.
Shares PD-1 blockade in tumors with mismatch-repair deficiency, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation, PD-1 and the tag colorectal-evidence.
Shares The consensus molecular subtypes of colorectal cancer, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation, Colorectal cancer and the tag colorectal-evidence.
Shares Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation, PD-1, Immune checkpoint inhibitors and the tag colorectal-evidence.
Shares Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation, Trial design, endpoints and cost, Colorectal cancer and the tag colorectal-evidence.
Shares Consensus molecular subtypes (CMS1-4), Biomarkers are not validated or standardised, Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation, Colorectal cancer and the tag colorectal-evidence.
Shares Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation, Colorectal cancer and the tag colorectal-evidence.