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.