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.
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Authors | Caroline Aspord, Alexander Pedroza-Gonzalez, Mike Gallegos, Sasha Tindle, Elizabeth C Burton, Dan Su, Florentina Marches, Jacques Banchereau, A Karolina Palucka |
Journal | The Journal of experimental medicine
(J Exp Med)
Vol. 204
Issue 5
Pg. 1037-47
(May 14 2007)
ISSN: 0022-1007 [Print] United States |
PMID | 17438063
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal
- Interleukin-13
- STAT6 Transcription Factor
- Interleukin-4
- Interferon-gamma
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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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