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Tumor-associated myeloid cells provide critical support for T-ALL.
Lyu, Aram; Triplett, Todd A; Nam, Seo Hee; Hu, Zicheng; Arasappan, Dhivya; Godfrey, Wesley H; Ames, Rachel Y; Sarang, Adviti; Selden, Hilary J; Lee, Chang-Han; Georgiou, George; Horton, Terzah M; Ehrlich, Lauren I R.
Afiliação
  • Lyu A; Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX.
  • Triplett TA; Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX.
  • Nam SH; Department of Oncology, Livestrong Cancer Institutes, The University of Texas at Austin Dell Medical School, Austin, TX.
  • Hu Z; Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX.
  • Arasappan D; Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA.
  • Godfrey WH; Center for Biomedical Research Support and.
  • Ames RY; Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX.
  • Sarang A; Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX.
  • Selden HJ; Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX.
  • Lee CH; Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX.
  • Georgiou G; Department of Chemical Engineering, The University of Texas at Austin, Austin, TX; and.
  • Horton TM; Department of Chemical Engineering, The University of Texas at Austin, Austin, TX; and.
  • Ehrlich LIR; Department of Pediatrics, Baylor College of Medicine/Dan L. Duncan Cancer Center and Texas Children's Cancer Center, Houston, TX.
Blood ; 136(16): 1837-1850, 2020 10 15.
Article em En | MEDLINE | ID: mdl-32845007
Despite harboring mutations in oncogenes and tumor suppressors that promote cancer growth, T-cell acute lymphoblastic leukemia (T-ALL) cells require exogenous cells or signals to survive in culture. We previously reported that myeloid cells, particularly dendritic cells, from the thymic tumor microenvironment support the survival and proliferation of primary mouse T-ALL cells in vitro. Thus, we hypothesized that tumor-associated myeloid cells would support T-ALL in vivo. Consistent with this possibility, in vivo depletion of myeloid cells results in a significant reduction in leukemia burden in multiple organs in 2 distinct mouse models of T-ALL and prolongs survival. The impact of the myeloid compartment on T-ALL growth is not dependent on suppression of antitumor T-cell responses. Instead, myeloid cells provide signals that directly support T-ALL cells. Transcriptional profiling, functional assays, and acute in vivo myeloid-depletion experiments identify activation of IGF1R as a critical component of myeloid-mediated T-ALL growth and survival. We identify several myeloid subsets that have the capacity to directly support survival of T-ALL cells. Consistent with mouse models, myeloid cells derived from human peripheral blood monocytes activate IGF1R and directly support survival of primary patient T-ALL cells in vitro. Furthermore, enriched macrophage gene signatures in published clinical samples correlate with inferior outcomes for pediatric T-ALL patients. Collectively, these data reveal that tumor-associated myeloid cells provide signals critical for T-ALL growth in multiple organs in vivo and implicate tumor-associated myeloid cells and associated signals as potential therapeutic targets.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Comunicação Celular / Células Mieloides / Leucemia-Linfoma Linfoblástico de Células T Precursoras / Microambiente Tumoral Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Blood Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Comunicação Celular / Células Mieloides / Leucemia-Linfoma Linfoblástico de Células T Precursoras / Microambiente Tumoral Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Blood Ano de publicação: 2020 Tipo de documento: Article