Breast cancer instructs dendritic cells to prime interleukin 13-secreting CD4+ T cells that facilitate tumor development
Por:
Aspord C., Pedroza-Gonzalez A., Gallegos M., Tindle S., Burton E.C., Su D., Marches F., Banchereau J., Palucka A.K.
Publicada:
1 ene 2007
Resumen:
We previously reported (Bell, D., P. Chomarat, D. Broyles, G. Netto, G.M. Harb, S. Lebecque, J. Valladeau, J. Davoust, K.A. Palucka, and J. Banchereau. 1999. J. Exp. Med. 190: 1417-1426) that breast cancer tumors are infiltrated with mature dendritic cells (DCs), which cluster with CD4+ T cells. We now show that CD4+ T cells infiltrating breast cancer tumors secrete type 1 (interferon ?) as well as high levels of type 2 (interleukin [IL] 4 and IL-13) cytokines. Immunofluorescence staining of tissue sections revealed intense IL-13 staining on breast cancer cells. The expression of phosphorylated signal transducer and activator of transcription 6 in breast cancer cells suggests that IL-13 actually delivers signals to cancer cells. To determine the link between breast cancer, DCs, and CD4+ T cells, we implanted human breast cancer cell lines in nonobese diabetic/LtSz-scid/scid ?2 microglobulin-deficient mice engrafted with human CD34+ hematopoietic progenitor cells and autologous T cells. There, CD4+ T cells promote early tumor development. This is dependent on DCs and can be partially prevented by administration of IL-13 antagonists. Thus, breast cancer targets DCs to facilitate its development. JEM © The Rockefeller University Press.
Filiaciones:
Aspord C.:
Baylor Institute for Immunology Research, Baylor National Institute of Allergy and Infectious Diseases, Cooperative Center for Translational Research on Human Immunology and Biodefense, United States
Pedroza-Gonzalez A.:
Baylor Institute for Immunology Research, Baylor National Institute of Allergy and Infectious Diseases, Cooperative Center for Translational Research on Human Immunology and Biodefense, United States
Gallegos M.:
Baylor Institute for Immunology Research, Baylor National Institute of Allergy and Infectious Diseases, Cooperative Center for Translational Research on Human Immunology and Biodefense, United States
Tindle S.:
Baylor Institute for Immunology Research, Baylor National Institute of Allergy and Infectious Diseases, Cooperative Center for Translational Research on Human Immunology and Biodefense, United States
Burton E.C.:
Department of Pathology, Baylor University Medical Center, Dallas, TX 75204, United States
Su D.:
Department of Pathology, Baylor University Medical Center, Dallas, TX 75204, United States
Marches F.:
Baylor Institute for Immunology Research, Baylor National Institute of Allergy and Infectious Diseases, Cooperative Center for Translational Research on Human Immunology and Biodefense, United States
Banchereau J.:
Baylor Institute for Immunology Research, Baylor National Institute of Allergy and Infectious Diseases, Cooperative Center for Translational Research on Human Immunology and Biodefense, United States
Palucka A.K.:
Baylor Institute for Immunology Research, Baylor National Institute of Allergy and Infectious Diseases, Cooperative Center for Translational Research on Human Immunology and Biodefense, United States
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