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Th1 cytokines in pediatric acute lymphoblastic leukemia.
Schober, Sarah; Rottenberger, Jennifer M; Hilz, Johannes; Schmid, Evi; Ebinger, Martin; Feuchtinger, Tobias; Handgretinger, Rupert; Lang, Peter; Queudeville, Manon.
Afiliación
  • Schober S; Department I - General Pediatrics, Hematology/Oncology, University Children's Hospital, Eberhard Karls University Tuebingen, Tuebingen, Germany.
  • Rottenberger JM; Department I - General Pediatrics, Hematology/Oncology, University Children's Hospital, Eberhard Karls University Tuebingen, Tuebingen, Germany.
  • Hilz J; Department I - General Pediatrics, Hematology/Oncology, University Children's Hospital, Eberhard Karls University Tuebingen, Tuebingen, Germany.
  • Schmid E; Department of Pediatric Surgery and Pediatric Urology, University Children's Hospital, Eberhard Karls University Tuebingen, Tuebingen, Germany.
  • Ebinger M; Department I - General Pediatrics, Hematology/Oncology, University Children's Hospital, Eberhard Karls University Tuebingen, Tuebingen, Germany.
  • Feuchtinger T; Dr. Von Hauner University Children's Hospital, LMU, Munich, Germany.
  • Handgretinger R; Department I - General Pediatrics, Hematology/Oncology, University Children's Hospital, Eberhard Karls University Tuebingen, Tuebingen, Germany.
  • Lang P; Department I - General Pediatrics, Hematology/Oncology, University Children's Hospital, Eberhard Karls University Tuebingen, Tuebingen, Germany.
  • Queudeville M; Department I - General Pediatrics, Hematology/Oncology, University Children's Hospital, Eberhard Karls University Tuebingen, Tuebingen, Germany. m.queudeville@uke.de.
Cancer Immunol Immunother ; 72(11): 3621-3634, 2023 Nov.
Article en En | MEDLINE | ID: mdl-37610672
Immune milieus play an important role in various types of cancer. The present study focuses on the effect of Th1 cytokines on pediatric acute lymphoblastic leukemia (ALL). The reaction of ALL cell lines and patient-derived xenografts (PDX) to the most important Th1 cytokines TNF-α (tumor necrosis factor alpha) and IFN-γ (interferon gamma) is analyzed and correlated with the respective cytokine receptors and the intracellular signaling molecules. ALL cell lines and ALL PDX display a great heterogeneity in cell death after incubation with TNF-α and IFN-γ. Several samples show a dose-dependent and additive induction of cell death by both cytokines; others do not react at all or even display an increased viability. Apoptosis is the main type of cell death induced by Th1 cytokines in ALL cells. Over all leukemia cells analyzed, IFN-γ receptor (IFNGR) shows a higher expression than both TNF-receptors, resulting in higher phosphorylation of STAT1 (signal transducer and activator of transcription) compared to phosphorylation of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B-cells) in the TNF pathway. The activation of STAT1 correlates with the amount of cell death after stimulation with Th1 cytokines. TNF-α and IFN-γ lead to heterogeneous reactions in ALL cell lines and ALL PDX but are able to induce cell death by apoptosis in the majority of ALL blasts. The correlation of a high expression of IFNGR and following activation of STAT1 with cell death indicates an important role for IFN-γ signaling in this setting.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Citocinas / Leucemia-Linfoma Linfoblástico de Células Precursoras Límite: Child / Humans Idioma: En Revista: Cancer Immunol Immunother Asunto de la revista: ALERGIA E IMUNOLOGIA / NEOPLASIAS / TERAPEUTICA Año: 2023 Tipo del documento: Article País de afiliación: Alemania

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Citocinas / Leucemia-Linfoma Linfoblástico de Células Precursoras Límite: Child / Humans Idioma: En Revista: Cancer Immunol Immunother Asunto de la revista: ALERGIA E IMUNOLOGIA / NEOPLASIAS / TERAPEUTICA Año: 2023 Tipo del documento: Article País de afiliación: Alemania
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