ArticleThe Journal of clinical investigation2001
IFN-gamma and Fas/FasL are required for the antitumor and antiangiogenic effects of IL-12/pulse IL-2 therapy.
Article in The Journal of clinical investigation, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
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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
42 citing papers in PubMed.
- Immunogene therapy of recurrent glioblastoma multiforme with a liposomally encapsulated replication-incompetent Semliki forest virus vector carrying the human interleukin-12 gene--a phase I/II clinical protocol.Journal of neuro-oncologyTrial
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- Immunotherapy for Renal Cell Carcinoma-What More is to Come?Targeted oncology · 2025Review
- Tumor-Localized Interleukin-2 and Interleukin-12 Combine with Radiation Therapy to Safely Potentiate Regression of Advanced Malignant Melanoma in Pet Dogs.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Tumor-localized interleukin-2 and interleukin-12 combine with radiation therapy to safely potentiate regression of advanced malignant melanoma in pet dogs.bioRxiv : the preprint server for biology · 2024Article
- Article
- Article
- Synthetic virology approaches to improve the safety and efficacy of oncolytic virus therapies.Nature communications · 2023Article
- Stem cells-derived natural killer cells for cancer immunotherapy: current protocols, feasibility, and benefits of ex vivo generated natural killer cells in treatment of advanced solid tumors.Cancer immunology, immunotherapy : CII · 2021Review
- Cancer testis antigen PRAME: An anti-cancer target with immunomodulatory potential.Journal of cellular and molecular medicine · 2021Article
- Natural Killer Cells: The Linchpin for Successful Cancer Immunotherapy.Frontiers in immunology · 2021Review
- Elevated VEGF-A & PLGF concentration in aqueous humor of patients with uveal melanoma following Iodine-125 plaque radiotherapy.International journal of ophthalmology · 2020Article
- Interleukin-armed chimeric antigen receptor-modified T cells for cancer immunotherapy.Gene therapy · 2018Review
- Epithelial-mesenchymal transition (EMT) signature is inversely associated with T-cell infiltration in non-small cell lung cancer (NSCLC).Scientific reports · 2018Article
- CD8 engineered cytotoxic T cells reprogram melanoma tumor environment.Oncoimmunology · 2016Article
- Structural Design of Engineered Costimulation Determines Tumor Rejection Kinetics and Persistence of CAR T Cells.Cancer cell · 2015Article
- The role of CD95 and CD95 ligand in cancer.Cell death and differentiation · 2015Review
- Mesenchymal stem cells genetically modified by lentivirus-mediated interleukin-12 inhibit malignant ascites in mice.Experimental and therapeutic medicine · 2014Article
- DICE: A novel tumor surveillance mechanism-a new therapy for cancer?Cell cycle (Georgetown, Tex.) · 2014Article
- Aging predisposes to acute inflammatory induced pathology after tumor immunotherapy.The Journal of experimental medicine · 2013Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Systemic administration of IL-12 and intermittent doses of IL-2 induce complete regression of metastatic murine renal carcinoma. Here, we show that overt tumor regression induced by IL-12/pulse IL-2 is preceded by recruitment of CD8(+) T cells, vascular injury, disrupted tumor neovascularization, and apoptosis of both endothelial and tumor cells. The IL-12/IL-2 combination synergistically enhances cell surface FasL expression on CD8(+) T lymphocytes in vitro and induces Fas and FasL expression within tumors via an IFN-gamma-dependent mechanism in vivo. This therapy also inhibits tumor neovascularization and induces tumor regression by mechanisms that depend critically on endogenous IFN-gamma production and an intact Fas/FasL pathway. The ability of IL-12/pulse IL-2 to induce rapid destruction of tumor-associated endothelial cells and regression of established metastatic tumors is ablated in mice with a dysregulated Fas/FasL pathway. The common, critical role for endogenous IFN-gamma and the Fas/FasL pathway in early antiangiogenic effects and in antitumor responses suggests that early, cytokine-driven innate immune mechanisms and CD8(+) T cell-mediated responses are interdependent. Definition of critical early molecular events engaged by IL-12/IL-2 may provide new perspective into optimal therapeutic engagement of a productive host-antitumor immune response.
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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.