ArticleJCI insight2018
IL-27 gene therapy induces depletion of Tregs and enhances the efficacy of cancer immunotherapy.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- Interleukin-27 remodels the bone marrow niche to suppress B-cell development and leukaemia progression in mouse models.EBioMedicine · 2026Article
- Reframing IL-27: a central regulator of CD8Trends in immunology · 2026Review
- The role of miRNAs in the development of Super-Tregs as a potential therapy for neurodegenerative diseases.Frontiers in immunology · 2026Review
- CD4Nature immunology · 2025Article
- Research status and future perspectives of IL‑27 in the treatment of stroke (Review).International journal of molecular medicine · 2025Review
- Oncolytic HSV-IL27 expression improves CD8 T cell function and therapeutic activity in syngeneic glioma models.Journal for immunotherapy of cancer · 2025Article
- Novel oncolytic vaccinia virus armed with interleukin-27 is a potential therapeutic agent for the treatment of murine pancreatic cancer.Journal for immunotherapy of cancer · 2025Article
- IL-27 elicits a cytotoxic CD8Nature · 2025Article
- Interleukins 30 and 27 in psoriasis and inflammation.Postepy dermatologii i alergologii · 2025Review
- Association between interleukin-27 and suicidal ideation: a Mendelian randomization analysis and peripheral blood experimental study.Frontiers in psychiatry · 2025Article
- Proximity-dependent labeling identifies dendritic cells that drive the tumor-specific CD4Science immunology · 2024Article
- IL-27 Gene Therapy Ameliorates IPEX Syndrome Caused by Germline Mutation of Foxp3 Gene: A Major Role for Induction of IL-10.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Current Trends and Innovative Approaches in Cancer Immunotherapy.AAPS PharmSciTech · 2024Review
- Highly expressed of BID indicates poor prognosis and mediates different tumor microenvironment characteristics in clear cell renal cell carcinoma.Discover oncology · 2024Article
- IL-27 Gene Therapy Induces Stat3-Mediated Expansion of CD11b+Gr1+ Myeloid Cells and Promotes Accumulation of M1 Macrophages in the Tumor Microenvironment.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Cytokine receptor IL27RA is an NF-κB-responsive gene involved in CD38 upregulation in multiple myeloma.Blood advances · 2023Article
- Interleukin gene delivery for cancer gene therapy:Iranian journal of basic medical sciences · 2023Review
- Enhancedanti-tumor efficacy through a combination of intramuscularly expressed DNA vaccine and plasmid-encoded PD-1 antibody.Frontiers in immunology · 2023Article
- Cabozantinib and IL-27 combinatorial therapy for bone-metastatic prostate cancer.Frontiers in molecular biosciences · 2023Article
- Promising therapeutic aspects in human genetic imprinting disorders.Clinical epigenetics · 2022Review
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Tumor-induced expansion of Tregs is a significant obstacle to cancer immunotherapy. However, traditional approaches to deplete Tregs are often inefficient, provoking autoimmunity. We show here that administration of IL-27-expressing recombinant adeno-associated virus (AAV-IL-27) significantly inhibits tumor growth and enhances T cell responses in tumors. Strikingly, we found that AAV-IL-27 treatment causes rapid depletion of Tregs in peripheral blood, lymphoid organs, and - most pronouncedly - tumor microenvironment. AAV-IL-27-mediated Treg depletion is dependent on IL-27 receptor and Stat1 in Tregs and is a combined result of CD25 downregulation in Tregs and inhibition of IL-2 production by T cells. In combination with a GM-CSF vaccine, AAV-IL-27 treatment not only induced nearly complete tumor rejection, but also resulted in amplified neoantigen-specific T cell responses. AAV-IL-27 also dramatically increased the efficacy of anti-PD-1 therapy, presumably due to induction of PD-L1 in T cells and depletion of Tregs. Importantly, AAV-IL-27 therapy did not induce significant adverse events, partially due to its induction of IL-10. In a plasmacytoma mouse model, we found that IL-10 was required for AAV-IL-27-mediated tumor rejection. Thus, our study demonstrates the potential of AAV-IL-27 as an independent cancer therapeutic and as an efficient adjuvant for cancer immunotherapy.
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