The Journal of Experimental Medicine
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Published online April 16, 2007
doi:10.1084/jem.20061120
The Journal of Experimental Medicine, Vol. 204, No. 5, 1037-1047
The Rockefeller University Press, 0022-1007 $30.00
© 2007 Aspord et al.
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ARTICLE

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

Caroline Aspord1, Alexander Pedroza-Gonzalez1, Mike Gallegos1, Sasha Tindle1, Elizabeth C. Burton2, Dan Su2, Florentina Marches1, Jacques Banchereau1, and A. Karolina Palucka1

1 Baylor Institute for Immunology Research and Baylor National Institute of Allergy and Infectious Diseases Cooperative Center for Translational Research on Human Immunology and Biodefense and 2 Department of Pathology, Baylor University Medical Center, Dallas, TX 75204

CORRESPONDENCE A. Karolina Palucka: karolinp{at}baylorhealth.edu

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 ß2 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.

Abbreviations used: CRTH2, chemoattractant receptor– homologous molecule expressed on Th2 cells; HPC, hematopoietic progenitor cell; Humouse, humanized mouse; NOD/SCID/ß2m–/–, nonobese diabetic/LtSz-scid/scid ß2 microglobulin–deficient; pSTAT6, phosphorylated STAT6; rh, recombinant human.


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