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Breast cancer instructs dendritic cells to prime interleukin 13-secreting CD4+ T cells that facilitate tumor development.

Abstract
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 gamma) 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 beta2 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.
AuthorsCaroline Aspord, Alexander Pedroza-Gonzalez, Mike Gallegos, Sasha Tindle, Elizabeth C Burton, Dan Su, Florentina Marches, Jacques Banchereau, A Karolina Palucka
JournalThe Journal of experimental medicine (J Exp Med) Vol. 204 Issue 5 Pg. 1037-47 (May 14 2007) ISSN: 0022-1007 [Print] United States
PMID17438063 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Monoclonal
  • Interleukin-13
  • STAT6 Transcription Factor
  • Interleukin-4
  • Interferon-gamma
Topics
  • Animals
  • Antibodies, Monoclonal (therapeutic use)
  • Breast Neoplasms (drug therapy, immunology, physiopathology)
  • CD4-Positive T-Lymphocytes (metabolism)
  • Dendritic Cells (metabolism)
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Interferon-gamma (metabolism)
  • Interleukin-13 (immunology, metabolism)
  • Interleukin-4 (metabolism)
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • STAT6 Transcription Factor (metabolism)
  • Signal Transduction (immunology)

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