Trial reportGut2025
CAF-macrophage crosstalk in tumour microenvironments governs the response to immune checkpoint blockade in gastric cancer peritoneal metastases.
Trial report in Gut, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
120 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Impact of metastatic pattern and histologic subtype on PD-(L)1 inhibitor efficacy in HER2-negative advanced gastric and gastroesophageal cancer: a meta-analysis.Frontiers in oncology · 2026Pooled it
- Trial
- Multifaceted roles of chemokines in gastric cancer: From tumor microenvironment modulation to therapeutic targeting (Review).Oncology letters · 2026Review
- Tumor microenvironment and gut microbiome in immunotherapy resistance in gastric cancer: clinical questions, biological mechanisms, and evidence-based therapeutic perspectives.Medical oncology (Northwood, London, England) · 2026Review
- Molecular classification and precision therapy in gastric cancer: Current advances and future perspectives (Review).Oncology reports · 2026Review
- Article
- Deubiquitinase USP48 Promotes Gastric Cancer Peritoneal Metastasis by Stabilizing S100A9 to Drive Neutrophil Extracellular Traps Formation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Review
- Intratumoral PD-1Medical oncology (Northwood, London, England) · 2026Article
- Stage-Specific Mucin Reprogramming Across the Gastric Cancer Cascade: Unveiling Molecular Mechanisms and Novel Therapeutic Vulnerabilities.Biomolecules · 2026Review
- Tissue-Resident Macrophage in Inflammation and Cancer.MedComm · 2026Review
- FAPExperimental & molecular medicine · 2026Article
- Fusion-driven oncogenic programs shape the immune landscape in translocation renal cell carcinoma.Nature communications · 2026Article
- Multi-omics-driven precision medicine.iMeta · 2026Review
- Mutant TP53 hijacks RNA-splicing factor RBM28 to suppress double-stranded RNA triggered antitumor immunity.Nature communications · 2026Article
- Overcoming resistance to immune checkpoint inhibitors in cancer: translational mechanisms, dynamic biomarkers, clinically actionable combination strategies, and comparative checkpoint biology.Immunologic research · 2026Review
- Predictors of immunotherapy response in gastric cancer: the role of the tumor microenvironment and integrative predictive models.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Immune niche composed of C1QNature communications · 2026Article
- Conversion surgery after immunotherapy and chemotherapy for gastric cancer with peritoneal metastasis or positive peritoneal cytology: A retrospective cohort study.Chinese medical journal · 2026Article
- Cancer drug response and resistance: molecular mechanisms and combating strategies.Signal transduction and targeted therapy · 2026Review
60 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPeritoneal metastasis is the most common metastasis pattern of gastric cancer. Patients with gastric cancer peritoneal metastasis (GCPM) have a poor prognosis and respond poorly to conventional treatments. Recently, immune checkpoint blockade (ICB) has demonstrated favourable efficacy in the treatment of GCPM. Stratification of best responders and elucidation of resistance mechanisms of ICB therapies are highly important and remain major clinical challenges.
designWe performed a phase II trial involving patients with GCPM treated with ICB (sintilimab) combined with chemotherapy. The samples of primary tumours, GCPMs and peripheral blood from patients were collected for single-cell sequencing to comprehensively interpret the tumour microenvironment of GCPM and its impacts on immunotherapy efficacy.
resultsThe GCPM ecosystem coordinates a unique immunosuppressive pattern distinct from that of primary GC, which is dominated by a stroma-myeloid niche composed of SPP1+tumour-associated macrophages (TAMs) and Thrombospondin 2 (THBS2)+matrix cancer-associated fibroblasts (mCAFs). Consequently, this stroma-myeloid crosstalk is the major mediator of ICB resistance in patients with GCPM. Mechanistically, the accumulated THBS2+mCAFs facilitate the recruitment of peritoneum-specific tissue-resident macrophages and their transformation into SPP1+TAMs via the complement C3 and its receptor C3a receptor 1 (C3AR1), thereby forming a protumoral stroma-myeloid niche. Blocking the C3-C3AR1 axis disrupts the stroma-myeloid crosstalk and thereby significantly improves the benefits of ICB in
conclusionOur findings provide a new molecular portrait of cell compositions associated with ICB resistance in patients with GCPM and aid in the prioritisation of therapeutic candidates to potentiate immunotherapy.
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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.