Our studies showed that tumor-infiltrating dendritic cells (DCs) in breast cancer drive inflammatory T helper 2 (iTh2) cells and pro-tumor inflammation. Here we show that intratumoral delivery of the b-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 ligation of dectin-1, which become resistant to cancer-derived thymic stromal lymphopoietin (TSLP), produce IL12p70 and favor the generation of T helper 1 (Th1) cells. DCs activated via dectin-1, but not those activated with TLR-7/8 ligand or poly IC, 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 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 humanized mice 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.
- Received December 5, 2013.
- Revision received January 29, 2014.
- Accepted February 20, 2014.
- Copyright © 2014, American Association for Cancer Research.