ArticleJournal of experimental & clinical cancer research : CR2023
Cancer-associated fibroblasts-derived CXCL12 enhances immune escape of bladder cancer through inhibiting P62-mediated autophagic degradation of PDL1.
Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 79 citations in OpenAlex.
- Platelets as non-canonical immune regulatory nodes: orchestrating T cell dysfunction and immunotherapy resistance in cancer.Apoptosis : an international journal on programmed cell death · 2026Review
- Metabolic Reprogramming in Bladder Cancer: Molecular Drivers, Immune Regulation and Therapeutic Opportunities.Cancers · 2026Review
- Integrated scRNA-Seq and Spatial Transcriptomics Reveal CHPF and GPC1 as Markers of Cancer-Associated Fibroblast-Dominant Domains in Colorectal Cancer.Cancer medicine · 2026Article
- Heterogeneity in cancer: molecular mechanisms and therapeutic strategies.Signal transduction and targeted therapy · 2026Review
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- A machine learning-guided epithelial plasticity score refines prognostication and immune-context stratification in muscle-invasive bladder cancer.Discover oncology · 2026Article
- NOTCH3 regulates myofibroblastic CAF differentiation via the P62-ROS signaling axis to promote bladder cancer progression.Journal of experimental & clinical cancer research : CR · 2026Article
- Glycolysis-driven cancer-associated fibroblasts shape T-Cell exclusion via the CXCL16-CXCR6 Axis: a metabolic-chemokine mechanism in tumor immunity.Journal of translational medicine · 2026Review
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- Cytokines and cancer-associated fibroblasts.Journal of hematology & oncology · 2026Review
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- Effects of Tumor Microenvironment on Lung Cancer Stem Cells: Bidirectional Regulatory Mechanisms.Cancer medicine · 2026Review
- RBX1Cancers · 2026Article
- Spatially defined danger zone shapes gastric cancer progression through CCDC80Apoptosis : an international journal on programmed cell death · 2026Article
- Ferroptosis-autophagy crosstalk in bladder cancer: mechanisms and therapeutic implications.Molecular cancer · 2026Review
- The Significance of the Heterogeneity of Cancer-Associated Fibroblasts in Tumor Microenvironments.Metabolites · 2026Review
- RT-ICI therapy induces a distal immunometabolic axis that shapes systemic macrophage polarization and enhances local T cell immunity.Cell communication and signaling : CCS · 2026Article
- TRIM38 Suppresses Breast Cancer Progression via Modulating SQSTM1 Ubiquitination and Autophagic Flux.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cancer-associated fibroblasts: enablers of tumor drug resistance.Journal of translational medicine · 2026Review
- Single-cell and immune-context integration identifies basement-membrane/metastasis signatures that sharpen bladder-cancer diagnosis and prognosis.Discover oncology · 2026Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundCancer-associated fibroblasts (CAFs), the predominant stromal cell of tumor microenvironment (TME), play an important role in tumor progression and immunoregulation by remodeling extracellular matrix (ECM) and secreting cytokines. However, little is known about the details of the underlying mechanism in bladder cancer.
methodsBioinformatics analysis was performed to analyze the prognostic value of CAFs and CXCL12 using GEO, TCGA and SRA databases. The effects of CXCL12 on bladder cancer progression were investigated through in vitro and in vivo assays. The biological mechanism of the effect of CXCL12 on PDL1 were investigated using western blotting, immunoprecipitation, RT-PCR, immunofluorescence, mass spectrometry, protein stability, and flow cytometry.
resultsThe results demonstrated that CAFs-derived CXCL12 promoted cancer cell migration and invasion and upregulated PDL1. Mechanistically, upon binding to its specific receptor, CXCL12 activated the downstream JAK2/STAT3 pathway and rapidly up-regulated the expression of deubiquitinase CYLD. CYLD deubiquitinated P62 causing P62 accumulation, which in turn inhibited the autophagic degradation of PDL1. In vivo experiments demonstrated that blocking CXCL12 inhibited tumor growth, reduced tumor PDL1 expression and increased immune cell infiltration.
conclusionsThis study revealed a novel mechanism for the role of CXCL12 in P62-mediated PDL1 autophagic regulation. Combined application of CXCL12 receptor blocker and PD1/PDL1 blocker can more effectively inhibit PDL1 expression and enhance antitumor immune response. Targeting CAFs-derived CXCL12 may provide an effective strategy for immunotherapy in bladder cancer.
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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.