PT  - JOURNAL ARTICLE
AU  - Wu, Te-Chia
AU  - Xu, Kangling
AU  - Banchereau, Romain
AU  - Marches, Florentina
AU  - Yu, Chun I.
AU  - Martinek, Jan
AU  - Anguiano, Esperanza
AU  - Pedroza-Gonzalez, Alexander
AU  - Snipes, G. Jackson
AU  - O'Shaughnessy, Joyce
AU  - Nishimura, Stephen
AU  - Liu, Yong-Jun
AU  - Pascual, Virginia
AU  - Banchereau, Jacques
AU  - Oh, Sangkon
AU  - Palucka, Karolina
TI  - Reprogramming Tumor-Infiltrating Dendritic Cells for CD103<sup>+</sup>CD8<sup>+</sup> Mucosal T-cell Differentiation and Breast Cancer Rejection
AID  - 10.1158/2326-6066.CIR-13-0217
DP  - 2014 May 01
TA  - Cancer Immunology Research
PG  - 487--500
VI  - 2
IP  - 5
4099  - http://cancerimmunolres.aacrjournals.org/content/2/5/487.short
4100  - http://cancerimmunolres.aacrjournals.org/content/2/5/487.full
SO  - Cancer Immunol Res2014 May 01; 2
AB  - Our studies showed that tumor-infiltrating dendritic cells (DC) in breast cancer drive inflammatory Th2 (iTh2) cells and protumor inflammation. Here, we show that intratumoral delivery of the β-glucan curdlan, a ligand of dectin-1, blocks the generation of iTh2 cells and prevents breast cancer progression in vivo. Curdlan reprograms tumor-infiltrating DCs via the ligation of dectin-1, enabling the DCs to become resistant to cancer-derived thymic stromal lymphopoietin (TSLP), to produce IL-12p70, and to favor the generation of Th1 cells. DCs activated via dectin-1, but not those activated with TLR-7/8 ligand or poly I:C, induce CD8+ T cells to express CD103 (αE integrin), a ligand for cancer cells, E-cadherin. Generation of these mucosal CD8+ T cells is regulated by DC-derived integrin αvβ8 and TGF-β activation in a dectin-1–dependent fashion. These CD103+CD8+ mucosal T cells accumulate in the tumors, thereby increasing cancer necrosis and inhibiting cancer progression in vivo in a humanized mouse model of breast cancer. Importantly, CD103+CD8+ mucosal T cells elicited by reprogrammed DCs can reject established cancer. Thus, reprogramming tumor-infiltrating DCs represents a new strategy for cancer rejection. Cancer Immunol Res; 2(5); 487–500. ©2014 AACR.