ArticleMolecular therapy : the journal of the American Society of Gene Therapy2013
Collapse of the tumor stroma is triggered by IL-12 induction of Fas.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- The Emerging World of TCR-T Cell Trials Against Cancer: A Systematic Review.Technology in cancer research & treatment · 2019Pooled it
- Interleukin-12 Delivery Strategies and Advances in Tumor Immunotherapy.Current issues in molecular biology · 2024Review
- Short-term, nonsurgical periodontal therapy boosts interleukin-12 levels and reduces oral cancer risk.Irish journal of medical science · 2024Article
- Inhalable extracellular vesicle delivery of IL-12 mRNA to treat lung cancer and promote systemic immunity.Nature nanotechnology · 2024Article
- Hypoxia-regulated secretion of IL-12 enhances antitumor activity and safety of CD19 CAR-T cells in the treatment of DLBCL.Molecular therapy oncolytics · 2023Article
- Intratumourally injected alum-tethered cytokines elicit potent and safer local and systemic anticancer immunity.Nature biomedical engineering · 2022Article
- Mesenchymal stromal cells as carriers of IL-12 reduce primary and metastatic tumors of murine melanoma.Scientific reports · 2021Article
- Reactive myelopoiesis and the onset of myeloid-mediated immune suppression: Implications for adoptive cell therapy.Cellular immunology · 2021Review
- Enhanced efficacy and limited systemic cytokine exposure with membrane-anchored interleukin-12 T-cell therapy in murine tumor models.Journal for immunotherapy of cancer · 2020Article
- Potential strategies against resistance to CAR T-cell therapy in haematological malignancies.Therapeutic advances in medical oncology · 2020Review
- Resistance Mechanisms to CAR T-Cell Therapy and Overcoming Strategy in B-Cell Hematologic Malignancies.International journal of molecular sciences · 2019Review
- TGF-β Inhibitors in Metastatic Pancreatic Ductal Adenocarcinoma.Journal of gastrointestinal cancer · 2019Review
- Development of CAR T cells designed to improve antitumor efficacy and safety.Pharmacology & therapeutics · 2017Review
- Advanced new strategies for metastatic cancer treatment by therapeutic stem cells and oncolytic virotherapy.Oncotarget · 2016Review
- The future of cancer treatment: immunomodulation, CARs and combination immunotherapy.Nature reviews. Clinical oncology · 2016Review
- CD8 engineered cytotoxic T cells reprogram melanoma tumor environment.Oncoimmunology · 2016Article
- Safety and antitumor effect of oncolytic and helper-dependent adenoviruses expressing interleukin-12 variants in a hamster pancreatic cancer model.Gene therapy · 2015Article
- Adoptive Cell Therapy--Tumor-Infiltrating Lymphocytes, T-Cell Receptors, and Chimeric Antigen Receptors.Seminars in oncology · 2015Review
- Dendritic Cells in Irradiated Mice Trigger the Functional Plasticity and Antitumor Activity of Adoptively Transferred Tc17 Cells via IL12 Signaling.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Article
- New insights into IL-12-mediated tumor suppression.Cell death and differentiation · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Engineering CD8⁺ T cells to deliver interleukin 12 (IL-12) to the tumor site can lead to striking improvements in the ability of adoptively transferred T cells to induce the regression of established murine cancers. We have recently shown that IL-12 triggers an acute inflammatory environment that reverses dysfunctional antigen presentation by myeloid-derived cells within tumors and leads to an increase in the infiltration of adoptively transferred antigen-specific CD8⁺ T cells. Here, we find that local delivery of IL-12 increased the expression of Fas within tumor-infiltrating macrophages, dendritic cells, and myeloid-derived suppressor cells (MDSC), and that these changes were abrogated in mice deficient in IL-12-receptor signaling. Importantly, upregulation of Fas in host mice played a critical role in the proliferation and antitumor activity of adoptively transferred IL-12-modified CD8⁺ T cells. We also observed higher percentages of myeloid-derived cell populations within tumors in Fas-deficient mice, indicating that tumor stromal destruction was dependent on the Fas death receptor. Taken together, these results describe the likely requirement for costimulatory reverse signaling through Fasl on T cells that successfully infiltrate tumors, a mechanism triggered by the induction of Fas expression on myeloid-derived cells by IL-12 and the subsequent collapse of the tumor stroma.
Indexed as
Identifiers
What OpenQuestion holds
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.