ArticleJournal for immunotherapy of cancer2024
Blocking senescence and tolerogenic function of dendritic cells induced by γδ Treg cells enhances tumor-specific immunity for cancer immunotherapy.
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 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- JAK/STAT-mediated regulation of PD-L1 expression in breast cancer: Molecular mechanisms and implications for immunotherapy.iScience · 2026Review
- Regulatory T cells in breast cancer drivers of immune suppression and targets for immunotherapy.Frontiers in immunology · 2026Review
- The promising cancer treatment approach in cancer immunotherapy: dendritic cell-based vaccines.Frontiers in immunology · 2026Review
- Bridging aging and colorectal cancer: synergistic roles of inflammaging and immunosenescence.Frontiers in immunology · 2026Review
- Review
- Irradiation‑induced cellular senescence is linked to pro‑survival signaling and checkpoint regulation in a 2D and 3D model for head and neck cancer.Oncology reports · 2025Article
- Mechanisms and Functions of γδ T Cells in Tumor Cell Recognition.Current oncology (Toronto, Ont.) · 2025Review
- Immune Modulation and Immunotherapy in Solid Tumors: Mechanisms of Resistance and Potential Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Tumor extracellular vesicle-derived PD-L1 promotes T cell senescence through lipid metabolism reprogramming.Science translational medicine · 2025Article
- Revealing the role of cancer-associated fibroblast senescence in prognosis and immune landscape in pancreatic cancer.iScience · 2025Article
- Differences in the peripheral blood immune landscape between early-onset and late-onset colorectal cancer.Frontiers in immunology · 2025Article
- Insights into tumor vaccines for elderly individuals in the context of immunosenescence.Frontiers in immunology · 2025Review
- Senescent immune cells in the tumor microenvironment: emerging insights into cancer immunotherapy resistance.Frontiers in immunology · 2025Review
- Clinicopathologic and Molecular Characterization of Colorectal Cancer in Patients Aged ≥80 years.Clinical interventions in aging · 2025Article
- MEGF8-driven metabolic reprogramming and immune evasion define a high-risk subtype of endometriosis-associated ovarian cancer.American journal of translational research · 2025Article
- The infection-microbiome-immunity axis in bladder cancer: mechanistic insights and therapeutic perspectives.Frontiers in immunology · 2025Review
- Review
- Gamma delta T cells in cancer therapy: from tumor recognition to novel treatments.Frontiers in medicine · 2024Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundRegulatory T (Treg) cells are a key component in maintaining the suppressive tumor microenvironment and immune suppression in different types of cancers. A precise understanding of the molecular mechanisms used by Treg cells for immune suppression is critical for the development of effective strategies for cancer immunotherapy.
methodsSenescence development and tolerogenic functions of dendritic cells (DCs) induced by breast cancer tumor-derived γδ Treg cells were fully characterized using real-time PCR, flow cytometry, western blot, and functional assays. Loss-of-function strategies with pharmacological inhibitor and/or neutralizing antibody were used to identify the potential molecule(s) and pathway(s) involved in DC senescence and dysfunction induced by Treg cells. Impaired tumor antigen HER2-specific recognition and immune response of senescent DCs induced by γδ Treg cells were explored in vitro and in vivo in humanized mouse models. In addition, the DC-based HER2 tumor vaccine immunotherapy in breast cancer models was performed to explore the enhanced antitumor immunity via prevention of DC senescence through blockages of STAT3 and programmed death-ligand 1 (PD-L1) signaling.
resultsWe showed that tumor-derived γδ Treg cells promote the development of senescence in DCs with tolerogenic functions in breast cancer. Senescent DCs induced by γδ Treg cells suppress Th1 and Th17 cell differentiation but promote the development of Treg cells. In addition, we demonstrated that PD-L1 and STAT3 signaling pathways are critical and involved in senescence induction in DCs mediated by tumor-derived γδ Treg cells. Importantly, our complementary in vivo studies further demonstrated that blockages of PD-L1 and/or STAT3 signaling can prevent γδ Treg-induced senescence and reverse tolerogenic functions in DCs, resulting in enhanced HER2 tumor-specific immune responses and immunotherapy efficacy in human breast cancer models.
conclusionsThese studies not only dissect the suppressive mechanism mediated by tumor-derived γδ Treg cells on DCs in the tumor microenvironment but also provide novel strategies to prevent senescence and dysfunction in DCs and enhance antitumor efficacy mediated by tumor-specific T cells for cancer immunotherapy.
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