ArticleCancer immunology, immunotherapy : CII2011
Mechanisms of T-cell protection from death by IRX-2: a new immunotherapeutic.
Article in Cancer immunology, immunotherapy : CII, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00210470 (A Phase 2, Open-label Trial of the Safety and Biological Effect of Subcutaneous IRX-2), which is not on this map. Cited by 19 papers.
What it found
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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.
A Phase 2, Open-label Trial of the Safety and Biological Effect of Subcutaneous IRX-2 (With Cyclophosphamide, Indomethacin, and Zinc) in Patients With Resectable Cancer of the Head and Neck
Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Increased lymphocyte infiltration in patients with head and neck cancer treated with the IRX-2 immunotherapy regimen.Cancer immunology, immunotherapy : CII · 2012Trial
- Peri-lymphatic cytokines (IRX-2) as immunologic induction preceding neoadjuvant chemo-immunotherapy in triple-negative breast cancer.NPJ breast cancer · 2026Article
- Tumor-derived vesicles in immune modulation: focus on signaling pathways.Frontiers in immunology · 2025Review
- Review
- The potential role of tumor-derived exosomes in diagnosis, prognosis, and response to therapy in cancer.Expert opinion on biological therapy · 2021Article
- Multiplex immunofluorescence to measure dynamic changes in tumor-infiltrating lymphocytes and PD-L1 in early-stage breast cancer.Breast cancer research : BCR · 2021Article
- Exosomes as mediators of immune regulation and immunotherapy in cancer.The FEBS journal · 2021Review
- Small extracellular vesicles containing arginase-1 suppress T-cell responses and promote tumor growth in ovarian carcinoma.Nature communications · 2019Observational
- IRX-2 natural cytokine biologic for immunotherapy in patients with head and neck cancers.OncoTargets and therapy · 2018Review
- Exosome-Based Cell-Cell Communication in the Tumor Microenvironment.Frontiers in cell and developmental biology · 2018Review
- Suppression of Lymphocyte Functions by Plasma Exosomes Correlates with Disease Activity in Patients with Head and Neck Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Exosomes and tumor-mediated immune suppression.The Journal of clinical investigation · 2016Review
- Tumor-Derived Exosomes and Their Role in Cancer Progression.Advances in clinical chemistry · 2016Review
- Prognostic impact of expression of Bcl-2 and Bax genes in circulating immune cells derived from patients with head and neck carcinoma.Neoplasia (New York, N.Y.) · 2013Article
- Immune modulation of T-cell and NK (natural killer) cell activities by TEXs (tumour-derived exosomes).Biochemical Society transactions · 2013Review
- IRX-2, a novel immunotherapeutic, enhances and protects NK-cell functions in cancer patients.Cancer immunology, immunotherapy : CII · 2012Article
- Sensitivity of TRPM7 channels to Mg2+ characterized in cell-free patches of Jurkat T lymphocytes.American journal of physiology. Cell physiology · 2012Article
- Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
objectivesIRX-2 is a novel immunotherapeutic containing physiologic quantities of several cytokines which protects human T lymphocytes from tumor-induced or drug-induced apoptosis. Here, we investigate the mechanisms responsible for IRX-2-mediated protection of T lymphocytes exposed to tumor-derived microvesicles (TMV).
methodsJurkat cells or primary human T cells ± IRX-2 were co-incubated with TMV and then examined by flow cytometry or Western blots for expression of molecules regulating cell survival (FLIP, Bcl-2, Bcl-xL, Mcl-1) or death (Fas, caspase 8, caspase 9, Bax, Bid). ANX V binding, caspase activation or cytochrome c release were also measured ± cycloheximide (CHX) or ± the Akt-specific inhibitor. Jurkat cells transfected with the cFLIP gene were used to evaluate the role of cFLIP in IRX-2-mediated protection. Effects of CHX on IRX-2-mediated protection and activation of NF-κB upon the TMV/IRX-2 treatment were also measured.
resultsIRX-2 protected T cells from apoptosis by preventing Fas overexpression induced by TMV and blocking caspase 8 activation by up-regulating cFLIP. Jurkat cells overexpressing cFLIP were more resistant to TMV-induced apoptosis than the mock-transfected cells (p < 0.02). Signaling via the PI3K/Akt pathway, IRX-2 corrected the imbalance of pro- versus anti-apoptotic proteins induced by TMV and promoted NF-κB translocation to the nucleus. CHX abolished IRX-2-mediated protection in T cells, suggesting that IRX-2 induces de novo synthesis of one or more proteins that are required for protection.
conclusionsThis biologic may be therapeutically useful for protection of activated T cells from tumor-induced immune suppression and death.
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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.