ArticleGastroenterology2021
Immunogenomics of Colorectal Cancer Response to Checkpoint Blockade: Analysis of the KEYNOTE 177 Trial and Validation Cohorts.
Article in Gastroenterology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 1 of them a synthesis that pooled it.
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Who cites it
97 citing papers in PubMed, 1 synthesis or guideline pooled it, 133 citations in OpenAlex.
- Biomarkers to predict efficacy of immune checkpoint inhibitors in colorectal cancer patients: a systematic review and meta-analysis.Clinical and experimental medicine · 2024Pooled it
- Plasma arginine as a predictive biomarker for outcomes with immune checkpoint inhibition in metastatic colorectal cancer: a correlative analysis of the CCTG CO.26 trial.Journal for immunotherapy of cancer · 2024Trial
- Early Immune Remodeling Steers Clinical Response to First-Line Chemoimmunotherapy in Advanced Gastric Cancer.Cancer discovery · 2024Trial
- Pucotenlimab in patients with advanced mismatch repair-deficient or microsatellite instability-high solid tumors: A multicenter phase 2 study.Cell reports. Medicine · 2023Trial
- Modulating the gut microbiota to enhance immune checkpoint inhibitor efficacy in colorectal cancer: mechanisms, therapeutic strategies, and clinical perspectives.Gut microbes · 2026Review
- Targeting WIP1 reprograms immunosuppressive tumor microenvironment to potentiate immunotherapy response in colorectal cancer.Cell death and differentiation · 2026Article
- An immunogenomic classification of solid tumours reveals subtype-specific therapeutic vulnerabilities for immunotherapy.EBioMedicine · 2026Article
- Immunotherapy resistance in colorectal cancer: therapeutic strategies and biomarker-guided approaches.Cancer cell international · 2026Review
- TP53 mutation is associated with improved disease control in patients with advanced RAS wild-type colorectal adenocarcinoma treated with cetuximab and pembrolizumab.International journal of cancer · 2026Article
- Review
- Atlas of human gut-associated lymphoid tissue reveals immunomodulatory interactions of B cells.Science immunology · 2026Article
- CXCR3 signaling promotes Delta One T cell recruitment and antitumor efficacy in colorectal cancer.Journal for immunotherapy of cancer · 2026Article
- Reprogramming T cell-myeloid crosstalk overcomes immune resistance in colorectal cancer.Cell reports. Medicine · 2026Article
- Current Status of the Diagnosis and Treatment of Mismatch Repair Deficient Colorectal Cancer.Biomedicines · 2026Review
- Spatial omics in high-grade glioma: study design, analytical pitfalls, and standards for reproducible neuro-oncology.Acta neuropathologica communications · 2026Review
- Spatial predictors of response to chemo-immunotherapy in microsatellite stable metastatic colorectal cancer.Nature communications · 2026Article
- Review
- Neoadjuvant mFOLFOX6 plus camrelizumab and apatinib in colon cancer and biomarker research via spatiotemporal-omics profiling.NPJ precision oncology · 2026Article
- Tumor-infiltrating immature innate lymphoid cells in colorectal cancer are biased toward ILC1/tissue-resident NK cell differentiation.Nature communications · 2026Article
- Clinical and immunological implications of lymphocyte-activation gene 3 expression in metastatic colorectal cancer.Cancer immunology, immunotherapy : CII · 2026Article
37 more citing papers are in PubMed but not listed here.
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Authors and funding
29 authors at 8 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsColorectal cancer (CRC) shows variable response to immune checkpoint blockade, which can only partially be explained by high tumor mutational burden (TMB). We conducted an integrated study of the cancer tissue and associated tumor microenvironment (TME) from patients treated with pembrolizumab (KEYNOTE 177 clinical trial) or nivolumab to dissect the cellular and molecular determinants of response to anti- programmed cell death 1 (PD1) immunotherapy.
methodsWe selected multiple regions per tumor showing variable T-cell infiltration for a total of 738 regions from 29 patients, divided into discovery and validation cohorts. We performed multiregional whole-exome and RNA sequencing of the tumor cells and integrated these with T-cell receptor sequencing, high-dimensional imaging mass cytometry, detection of programmed death-ligand 1 (PDL1) interaction in situ, multiplexed immunofluorescence, and computational spatial analysis of the TME.
resultsIn hypermutated CRCs, response to anti-PD1 immunotherapy was not associated with TMB but with high clonality of immunogenic mutations, clonally expanded T cells, low activation of Wnt signaling, deregulation of the interferon gamma pathway, and active immune escape mechanisms. Responsive hypermutated CRCs were also rich in cytotoxic and proliferating PD1
conclusionsOur study clarified the limits of TMB as a predictor of response of CRC to anti-PD1 immunotherapy. It identified a population of antigen-presenting macrophages interacting with CD8 T cells that consistently segregate with response. We therefore concluded that anti-PD1 agents release the PD1-PDL1 interaction between CD8 T cells and macrophages to promote cytotoxic antitumor activity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.