ArticleNature communications2025
Munc13-4 mediates tumor immune evasion by regulating the sorting and secretion of PD-L1 via exosomes.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Harnessing tumor-associated exosomal aminopeptidase N as a dual-function tool for monitoring and tackling chemoresistance in gastric cancer.Cell communication and signaling : CCS · 2026Article
- S100A14 in Tumor-Derived EVs Targets PIAS3 to Reprogram Astrocytes and Induce Immunosuppressive Microenvironment Promoting Brain Metastasis and Germacrone Reversal Effect.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Parental gut microbiota dysbiosis is associated with cross-generationally shared DNA methylation patterns and autism-like behaviors in offspring.NPJ biofilms and microbiomes · 2026Article
- A Multi-omics Investigation Identifies TACC3 as a Driver of Immunosuppression in Intrahepatic Cholangiocarcinoma via Activation of the STAT3-PD-L1 Axis.Journal of clinical and translational hepatology · 2026Article
- Review
- Single-cell analysis of UNC13D-mediated immune and dedifferentiation heterogeneity in acute myeloid leukemia and development of a prognostic model.Translational cancer research · 2026Article
- Biomimetic Polymer-Based Nanomaterials for Immune-Responsive Hepatocellular Carcinoma Therapy.International journal of nanomedicine · 2026Review
- Nanosystem-Mediated Intercellular Crosstalk Modulation in the Tumor Microenvironment for Enhanced Cancer Immunotherapy.Drug design, development and therapy · 2026Review
- Exo-nanomaterials in cancer immunotherapy: reprogramming the tumor immune microenvironment.Frontiers in immunology · 2025Review
- Conditioned Media-Derived Tumor Extracellular Vesicles: Bridging Molecular Insights and Therapeutic Applications in Oncology.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnologyReview
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Authors and funding
11 authors.
Funding
Abstract
Tumor-derived exosomes carry programmed death-ligand 1 (PD-L1), which binds programmed cell death protein 1 (PD-1) on T cells, suppressing immune responses locally and systemically. However, the mechanisms governing exosomal PD-L1 sorting and secretion remain elusive. Here, we identify Munc13-4 as a crucial regulator of this process. Deletion of Munc13-4 in breast tumors enhances T cell-mediated anti-tumor immunity, suppresses tumor growth, and improves the efficacy of immune checkpoint inhibitors. Mechanistically, Munc13-4 collaborates with hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), Rab27, and SNAREs to facilitate PD-L1 sorting and secretion via exosomes. Cryogenic electron microscopy (cryo-EM) analysis of the Munc13-4-Rab27a complex provide structural insights into exosome secretion. Importantly, PD-L1 sorting relies on a ternary complex composed of Munc13-4, PD-L1 and HRS, which is regulated by interferon gamma (IFNγ) signaling. A designed peptide that disrupts Munc13-4-PD-L1 interaction impedes PD-L1 sorting, enhances antitumor immunity, and suppresses tumor growth, highlighting the therapeutic potential of targeting this pathway.
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