ArticleJournal of immunology (Baltimore, Md. : 1950)2012
Human prostate tumor antigen-specific CD8+ regulatory T cells are inhibited by CTLA-4 or IL-35 blockade.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 108 citations in OpenAlex.
- Immunotherapy as a Promising Treatment for Prostate Cancer: A Systematic Review.Journal of immunology research · 2017Pooled it
- CTLA-4: a promising immunosuppressive immune checkpoint in prostate cancer therapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- The Multifaceted Role ofGenes · 2025Review
- Lidocaine Modulates Cytokine Production and Reprograms the Tumor Immune Microenvironment to Enhance Anti-Tumor Immune Responses in Gastric Cancer.International journal of molecular sciences · 2025Article
- Prostate cancer immunotherapy-based strategies: an updated review emphasizing immune checkpoint inhibitors.Frontiers in immunology · 2025Review
- Urokinase-type plasminogen activator deficiency enhances CD8Frontiers in immunology · 2025Article
- Characterization of novel CD8Cellular and molecular life sciences : CMLS · 2024Article
- Tumor-derived interleukin 35 mediates the dissemination of gemcitabine resistance in pancreatic adenocarcinoma.Oncogene · 2024Article
- Review
- Dysfunction and regulatory interplay of T and B cells in chronic hepatitis B: immunotherapy and emerging antiviral strategies.Frontiers in cellular and infection microbiology · 2024Review
- Immunological facets of prostate cancer and the potential of immune checkpoint inhibition in disease management.Theranostics · 2024Review
- Human IL-35 Inhibits the Bioactivity of IL-12 and Its Interaction with IL-12Rβ2.ImmunoHorizons · 2023Article
- Pathogenesis and novel therapeutics of regulatory T cell subsets and interleukin-2 therapy in systemic lupus erythematosus.Frontiers in immunology · 2023Review
- A Mutated Prostatic Acid Phosphatase (PAP) Peptide-Based Vaccine Induces PAP-Specific CD8Cancers · 2022Article
- PD-L1iScience · 2022Article
- Gut microbiota-derived metabolite 3-idoleacetic acid together with LPS induces IL-35Microbiome · 2022Article
- Cytolytic CD4Frontiers in immunology · 2022Review
- Interleukin-35 in autoimmune dermatoses: Current concepts.Open medicine (Warsaw, Poland) · 2022Review
- What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 7: PD-L1 Expression in Liquid Biopsy.Journal of personalized medicine · 2021Review
- Interleukin-35: Structure, Function and Its Impact on Immune-Related Diseases.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2021Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Regulatory T cells play important roles in cancer development and progression by limiting the generation of innate and adaptive anti-tumor immunity. We hypothesized that in addition to natural CD4(+)CD25(+) regulatory T cells (Tregs) and myeloid-derived suppressor cells, tumor Ag-specific Tregs interfere with the detection of anti-tumor immunity after immunotherapy. Using samples from prostate cancer patients immunized with a DNA vaccine encoding prostatic acid phosphatase (PAP) and a trans-vivo delayed-type hypersensitivity (tvDTH) assay, we found that the detection of PAP-specific effector responses after immunization was prevented by the activity of PAP-specific regulatory cells. These regulatory cells were CD8(+)CTLA-4(+), and their suppression was relieved by blockade of CTLA-4, but not IL-10 or TGF-β. Moreover, Ag-specific CD8(+) Tregs were detected prior to immunization in the absence of PAP-specific effector responses. These PAP-specific CD8(+)CTLA-4(+) suppressor T cells expressed IL-35, which was decreased after blockade of CTLA-4, and inhibition of either CTLA-4 or IL-35 reversed PAP-specific suppression of tvDTH response. PAP-specific CD8(+)CTLA-4(+) T cells also suppressed T cell proliferation in an IL-35-dependent, contact-independent fashion. Taken together, these findings suggest a novel population of CD8(+)CTLA-4(+) IL-35-secreting tumor Ag-specific Tregs arise spontaneously in some prostate cancer patients, persist during immunization, and can prevent the detection of Ag-specific effector responses by an IL-35-dependent mechanism.
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Registered trials
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.