IRX-2, a novel immunotherapeutic, protects human T cells from tumor-induced cell death
| Autor: | Theresa L. Whiteside, Marta Szajnik, H Brandwein, Miroslaw J. Szczepanski, J W Hadden, J Han, K Signorelli, K Quadrini, Malgorzata Czystowska |
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| Přispěvatelé: | BMC, Ed., Centre de recherche Croissance et signalisation (UMR_S 845), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche Croissance et signalisation ( UMR_S 845 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) |
| Rok vydání: | 2009 |
| Předmět: |
Time Factors
MESH : Cytokines T-Lymphocytes medicine.medical_treatment MESH : Dose-Response Relationship Drug Apoptosis CD8-Positive T-Lymphocytes Fas ligand MESH: Dose-Response Relationship Drug MESH: Janus Kinase 3 Jurkat Cells Phosphatidylinositol 3-Kinases MESH: Jurkat Cells STAT5 Transcription Factor Cytotoxic T cell MESH : Jurkat Cells bcl-2-Associated X Protein MESH: Cytokines tofacitinib Bcl-2-Like Protein 11 MESH : STAT5 Transcription Factor MESH : CD8-Positive T-Lymphocytes MESH: CD8-Positive T-Lymphocytes MESH : Antineoplastic Agents MESH : Proto-Oncogene Proteins c-akt Cytokine MESH : Proto-Oncogene Proteins Cytokines MESH: Membrane Proteins JAK3 MESH : Apoptosis Regulatory Proteins MESH : Time Factors MESH : Janus Kinase 3 Programmed cell death MESH: Cell Line Tumor kidney transplantation Antineoplastic Agents [SDV.BC]Life Sciences [q-bio]/Cellular Biology Biology Article Cell Line Tumor Proto-Oncogene Proteins medicine Humans MESH: bcl-2-Associated X Protein [SDV.BC] Life Sciences [q-bio]/Cellular Biology Molecular Biology Protein kinase B PI3K/AKT/mTOR pathway MESH : T-Lymphocytes MESH: Humans Dose-Response Relationship Drug MESH : bcl-2-Associated X Protein MESH : Cell Line Tumor [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology MESH: Proto-Oncogene Proteins c-akt MESH: Apoptosis Regulatory Proteins MESH: Apoptosis MESH: STAT5 Transcription Factor MESH : Humans MESH: Time Factors MESH : Phosphatidylinositol 3-Kinases Janus Kinase 3 Membrane Proteins Cell Biology Molecular biology MESH: Proto-Oncogene Proteins MESH: T-Lymphocytes MESH : Membrane Proteins MESH: Phosphatidylinositol 3-Kinases MESH: Antineoplastic Agents Apoptosis Regulatory Proteins Proto-Oncogene Proteins c-akt MESH : Apoptosis CD8 |
| Zdroj: | Cell Death and Differentiation Cell Death and Differentiation, 2009, 16 (5), pp.708-18. ⟨10.1038/cdd.2008.197⟩ Cell Death and Differentiation, Nature Publishing Group, 2009, 16 (5), pp.708-18. ⟨10.1038/cdd.2008.197⟩ Cell Death and Differentiation, Nature Publishing Group, 2009, 16 (5), pp.708-18. 〈10.1038/cdd.2008.197〉 |
| ISSN: | 1476-5403 1350-9047 |
| DOI: | 10.1038/cdd.2008.197 |
| Popis: | International audience; IRX-2 is a cytokine-based biologic agent that has the potential to enhance antitumor immune responses. We investigated whether IRX-2 can protect T cells from tumor-induced apoptosis. Tumor-derived microvesicles (MV) expressing FasL were purified from supernatants of tumor cells and incubated with activated CD8(+) T cells. MV induced significant CD8(+) T-cell apoptosis, as evidenced by Annexin binding (64.4+/-6.4%), caspase activation (58.1+/-7.6%), a loss of mitochondrial membrane potential (82.9+/-3.9%) and DNA fragmentation. T-cell pretreatment with IRX-2 prevented apoptosis. IRX-2-mediated cytoprotection was dose and time dependent and was comparable to effects of IL-2, IL-7 or IL-15. IRX-2 prevented MV-induced downregulation of JAK3 and TCRzeta chain and induced STAT5 activation in T cells. IRX-2 prevented MV-induced Bax and Bim upregulation (P |
| Databáze: | OpenAIRE |
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