ArticleCancer science2014
Suppression of Tregs by anti-glucocorticoid induced TNF receptor antibody enhances the antitumor immunity of interferon-α gene therapy for pancreatic cancer.
Article in Cancer science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Resisting Resistance to Immune Checkpoint Therapy: A Systematic Review.International journal of molecular sciences · 2020Pooled it
- Targeted Therapy for Highly Desmoplastic and Immunosuppressive Tumor Microenvironment of Pancreatic Ductal Adenocarcinoma.Cancers · 2024Review
- Unveiling the immunosuppressive landscape of pancreatic ductal adenocarcinoma: implications for innovative immunotherapy strategies.Frontiers in oncology · 2024Review
- Prognostic Factors in Advanced Non-Small Cell Lung Cancer Patients Treated with Immunotherapy.Cancers · 2023Review
- Immune checkpoint blockade in pancreatic cancer: Trudging through the immune desert.Seminars in cancer biology · 2022Review
- The Role of Immunotherapy in Pancreatic Cancer.Current oncology (Toronto, Ont.) · 2022Review
- The Interplay Between Inflammation and Stromal Components in Pancreatic Cancer.Frontiers in immunology · 2022Review
- Review
- Tumor resident regulatory T cells.Seminars in immunology · 2021Review
- RNA binding protein PCBP1 is an intracellular immune checkpoint for shaping T cell responses in cancer immunity.Science advances · 2020Article
- Intratumoral IFN-α gene delivery reduces tumor-infiltrating regulatory T cells through the downregulation of tumor CCL17 expression.Cancer gene therapy · 2019Article
- Pancreatic Cancer and Immunotherapy: Resistance Mechanisms and Proposed Solutions.Journal of gastrointestinal cancer · 2019Review
- Armed oncolytic viruses: A kick-start for anti-tumor immunity.Cytokine & growth factor reviews · 2018Review
- Hsp70 and gama-Semino protein as possible prognostic marker of prostate cancer.Frontiers in bioscience (Landmark edition) · 2018Review
- Next generation immune-checkpoints for cancer therapy.Journal of thoracic disease · 2018Review
- Immunomodulatory and antitumor effects of type I interferons and their application in cancer therapy.Oncotarget · 2017Review
- CAR T-cell therapy for pancreatic cancer.Journal of surgical oncology · 2017Review
- Subdiaphragmatic vagotomy promotes tumor growth and reduces survival via TNFα in a murine pancreatic cancer model.Oncotarget · 2017Article
- T-cell programming in pancreatic adenocarcinoma: a review.Cancer gene therapy · 2017Review
- Monoclonal Antibody Therapies for Hematological Malignancies: Not Just Lineage-Specific Targets.Frontiers in immunology · 2017Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have reported that interferon (IFN)-α can attack cancer cells by multiple antitumor mechanisms including the induction of direct cancer cell death and the enhancement of an immune response in several pancreatic cancer models. However, an immunotolerant microenvironment in the tumors is often responsible for the failure of the cancer immunotherapy. Here we examined whether the suppression of regulatory T cells (Tregs) within tumors can enhance an antitumor immunity induced by an intratumoral IFN-α gene transfer. First we showed that an intraperitoneal administration of an agonistic anti-glucocorticoid induced TNF receptor (GITR) monoclonal antibody (mAb), which is reported to suppress the function of Tregs, significantly inhibited subcutaneous tumor growth in a murine pancreatic cancer model. The anti-GITR mAb was then combined with the intratumoral injection of the IFN-α-adenovirus vector. The treatment with the antibody synergistically augmented the antitumor effect of IFN-α gene therapy not only in the vector-injected tumors but also in the vector-uninjected tumors. Immunostaining showed that the anti-GITR mAb decreased Foxp3(+) cells infiltrating in the tumors, while the intratumoral IFN-α gene transfer increased CD4(+) and CD8(+) T cells in the tumors. Therefore, the combination therapy strongly inclined the immune balance of the tumor microenvironment in an antitumor direction, leading to a marked systemic antitumor effect. The CCR5 expression on Tregs was downregulated in the antibody-treated mice, which may explain the decrease of tumor-infiltrating Tregs. The combination of Treg-suppression by GITR mAb and the tumor immunity induction by IFN-α gene therapy could be a promising therapeutic strategy for pancreatic cancer.
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Registered trials
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