ArticleJournal for immunotherapy of cancer2026
Hyaluronic acid-CD44 signaling defines therapeutic resistance and immunosuppressive microenvironment in peritoneal metastasis of gastric cancer.
Article in Journal for immunotherapy of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Beyond density: mapping the functional landscapes of macrophage-T lymphocyte niches in the tumor microenvironment.Frontiers in immunology · 2026Review
- Single-cell Transcriptomics Uncovers the Tumor Microenvironment and Collagen-CD44 Axis in HIV Positive Cervical Squamous Cell Carcinoma.Journal of Cancer · 2026Article
- Therapy-educated fibroblast states link treatment pressure to residual disease and acquired resistance in gastric cancer.Frontiers in immunology · 2026Review
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Authors and funding
19 authors.
Funding
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Abstract
backgroundPeritoneal metastasis (PM) is one of the most challenging clinical problems in gastric cancer (GC), largely due to its high recurrence rate and poor response to current therapies. Increasing evidence indicates that remodeling of the extracellular matrix (ECM) plays an important role in therapeutic failure. However, how specific stromal-immune interactions contribute to PM heterogeneity and immunotherapy resistance remains unclear. In this study, we investigated how ECM composition-particularly the accumulation of hyaluronic acid (HA)-influences the immune microenvironment and therapeutic responses in GC-associated PM.
methodsWe combined histopathological assessment, analyses of patient-derived specimens, single-cell transcriptomic profiling, and murine models of PM to delineate ECM remodeling patterns and immune cell dynamics in therapy-sensitive and therapy-resistant lesions. In addition, functional assays and pharmacological approaches were used to examine HA-CD44 signaling and its impact on CD4
resultsTherapy-sensitive PM lesions were characterized by enrichment of elastic fibers, whereas therapy-resistant lesions showed collagen accumulation. Notably, HA deposition emerged as a key feature distinguishing these ECM states and was closely associated with differential therapeutic outcomes. Elevated HA levels activated CD44-dependent signaling in CD4
conclusionsOur findings identify HA-CD44 signaling as a critical link between ECM remodeling and immune evasion in GC PM. Targeting ECM-driven immunosuppressive mechanisms may represent a promising strategy to overcome therapeutic resistance and improve the efficacy of immunotherapy in this aggressive disease.
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