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Histidine decarboxylase (HDC)-expressing granulocytic myeloid cells induce and recruit Foxp3+ regulatory T cells in murine colon cancer.
Chen, Xiaowei; Takemoto, Yoshihiro; Deng, Huan; Middelhoff, Moritz; Friedman, Richard A; Chu, Timothy H; Churchill, Michael J; Ma, Yan; Nagar, Karan K; Tailor, Yagnesh H; Mukherjee, Siddhartha; Wang, Timothy C.
Afiliação
  • Chen X; Division of Digestive and Liver Disease, Department of Medicine and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center , New York, NY, USA.
  • Takemoto Y; Division of Digestive and Liver Disease, Department of Medicine and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA; Department of Surgery and Clinical Science, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi, Japan.
  • Deng H; Division of Digestive and Liver Disease, Department of Medicine and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA; Department of Pathology, the Fourth Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
  • Middelhoff M; Division of Digestive and Liver Disease, Department of Medicine and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center , New York, NY, USA.
  • Friedman RA; Department of Biomedical Informatics and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center , New York, NY, USA.
  • Chu TH; Division of Digestive and Liver Disease, Department of Medicine and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center , New York, NY, USA.
  • Churchill MJ; Division of Hematology/Oncology, Department of Medicine and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center , New York, NY, USA.
  • Ma Y; Division of Hematology/Oncology, Department of Medicine and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center , New York, NY, USA.
  • Nagar KK; Division of Digestive and Liver Disease, Department of Medicine and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center , New York, NY, USA.
  • Tailor YH; Division of Digestive and Liver Disease, Department of Medicine and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center , New York, NY, USA.
  • Mukherjee S; Division of Hematology/Oncology, Department of Medicine and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center , New York, NY, USA.
  • Wang TC; Division of Digestive and Liver Disease, Department of Medicine and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center , New York, NY, USA.
Oncoimmunology ; 6(3): e1290034, 2017.
Article em En | MEDLINE | ID: mdl-28405523
ABSTRACT
The colorectal tumor microenvironment contains a diverse population of myeloid cells that are recruited and converted to immunosuppressive cells, thus facilitating tumor escape from immunoediting. We have identified a genetically and functionally distinct subset of dynamic bone marrow myeloid cells that are characterized by histidine decarboxylase (HDC) expression. Lineage tracing in Hdc-CreERT2;R26-LSL-tdTomato mice revealed that in homeostasis, there is a strong bias by HDC+ myeloid cells toward the CD11b+Ly6Ghi granulocytic lineage, which was accelerated during azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colonic carcinogenesis. More importantly, HDC+ myeloid cells strongly promoted colonic tumorigenesis, and colon tumor progression was profoundly suppressed by diphtheria toxin A (DTA)-mediated depletion of HDC+ granulocytic myeloid cells. In addition, tumor infiltration by Foxp3+ regulatory T cells (Tregs) was markedly impaired following HDC+ myeloid cell depletion. We identified an HDC+ myeloid-derived Cxcl13/Cxcr5 axis that mediated Foxp3 expression and Treg proliferation. Ablation of HDC+ myeloid cells or disruption of the Cxcl13/Cxcr5 axis by gene knockdown impaired the production and recruitment of Tregs. Cxcl13 induction of Foxp3 expression in Tregs during tumorigenesis was associated with Stat3 phosphorylation. Overall, HDC+ granulocytic myeloid cells affect CD8+ T cells directly and indirectly through the modulation of Tregs and thus appear to play key roles in suppressing tumoricidal immunity.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2017 Tipo de documento: Article