ArticleJournal for immunotherapy of cancer2024
EBV promotes TCR-T-cell therapy resistance by inducing CD163+M2 macrophage polarization and MMP9 secretion.
Article in Journal for immunotherapy of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Laryngeal squamous cell carcinoma: a functional "two-hit" model of papillomavirus-Epstein-Barr virus synergistic carcinogenesis.Frontiers in cellular and infection microbiology · 2026Pooled it
- EBV hijacks the metabolic function of CD73 to resist the antitumor function of NK cells.NPJ precision oncology · 2026Article
- Macrophages in oncoviral infections: from immune regulators to therapeutic targets.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Breathing new life into T-cell receptor-engineered T-cell therapy in solid tumors: enhancing strategies to expand the universality of precision therapy.Experimental hematology & oncology · 2026Review
- Exhausted CD8⁺ T cells promote ovarian cancer immunosuppression via CCL3-Driven M2 macrophage polarization.Cell death & disease · 2026Article
- T cell fate regulation in EBV‑associated nasopharyngeal carcinoma (Review).Oncology reports · 2026Review
- T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Recent advances in Epstein-Barr virus vaccines development from mechanistic exploration to clinical translation.NPJ vaccines · 2026Review
- Prognostic and Predictive Value of CD163+ Macrophages for Neoadjuvant Chemotherapy in Osteosarcoma.Biomedicines · 2026Article
- M2-polarized tumor-associated macrophages as key orchestrators of gastric cancer pathogenesis and therapeutic resistance.Discover oncology · 2026Review
- Modulating tumor-associated macrophages through APP-CD74 blockade with IL4R-exosomes synergizes with PD-1 inhibition in gastric cancer.NPJ precision oncology · 2026Article
- Harnessing the immune microenvironment: advances in nasopharyngeal carcinoma immunotherapy.Cell death discovery · 2026Review
- Immune Exhaustion in Chronic Infection and Cancer: Signaling Pathways and Therapeutic Interventions.MedComm · 2026Review
- The Caspase-1-EGR4 axis regulates macrophage repolarization in acute myeloid leukemia cells.Scientific reports · 2026Article
- Tumor neoantigen gene C7orf50 remodels the immune microenvironment by recruiting tumor-associated macrophages to promote hepatocellular carcinoma progression and lung metastasis.Journal for immunotherapy of cancer · 2026Article
- Integrated network toxicology, molecular docking, and molecular dynamics simulation reveals mechanisms of benzo[a]pyrene-induced pan-cancer.BMC pharmacology & toxicology · 2026Article
- Mechanical Microenvironment in Tumor Immune Evasion: Bidirectional Regulation Between Matrix Stiffness and Immune Cells and Its Therapeutic Implications.International journal of biological sciences · 2026Review
- Epstein-Barr virus associated diseases: Immune alterations and targeted approaches.Frontiers in immunology · 2026Review
- Dual immune armies in glaucoma: microglia and monocyte-derived macrophages.Frontiers in immunology · 2026Review
- Epstein-Barr virus-associated tumors: commonalities in pathogenesis and the tumor immune microenvironment.Frontiers in immunology · 2026Review
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21 authors.
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Abstract
backgroundEpstein-Barr virus (EBV) is a double-stranded DNA oncogenic virus. Several types of solid tumors, such as nasopharyngeal carcinoma, EBV-associated gastric carcinoma, and lymphoepithelioma-like carcinoma of the lung, have been linked to EBV infection. Currently, several TCR-T-cell therapies for EBV-associated tumors are in clinical trials, but due to the suppressive immune microenvironment of solid tumors, the clinical application of TCR-T-cell therapy for EBV-associated solid tumors is limited. Figuring out the mechanism by which EBV participates in the formation of the tumor immunosuppressive microenvironment will help T cells or TCR-T cells break through the limitation and exert stronger antitumor potential.
methodsFlow cytometry was used for analyzing macrophage differentiation phenotypes induced by EBV-infected and EBV-uninfected tumors, as well as the function of T cells co-cultured with these macrophages. Xenograft model in mice was used to explore the effects of M2 macrophages, TCR-T cells, and matrix metalloprotein 9 (MMP9) inhibitors on the growth of EBV-infected tumors.
resultsEBV-positive tumors exhibited an exhaustion profile of T cells, despite the presence of a large T-cell infiltration. EBV-infected tumors recruited a large number of mononuclear macrophages with CCL5 and induced CD163+M2 macrophages polarization through the secretion of CSF1 and the promotion of autocrine IL10 production by mononuclear macrophages. Massive secretion of MMP9 by this group of CD163+M2 macrophages induced by EBV infection was an important factor contributing to T-cell exhaustion and TCR-T-cell therapy resistance in EBV-positive tumors, and the use of MMP9 inhibitors improved the function of T cells cocultured with M2 macrophages. Finally, the combination of an MMP9 inhibitor with TCR-T cells targeting EBV-positive tumors significantly inhibited the growth of xenografts in mice.
conclusionsMMP9 inhibitors improve TCR-T cell function suppressed by EBV-induced M2 macrophages. TCR-T-cell therapy combined with MMP9 inhibitors was an effective therapeutic strategy for EBV-positive solid tumors.
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