Reprogramming Tumor-Infiltrating Dendritic Cells for CD103+CD8+ Mucosal T-cell Differentiation and Breast Cancer Rejection.
Document Type
Article
Publication Date
5-2014
JAX Location
Reprint Collection
JAX Source
Cancer Immunol Res 2014 May 2(5):487-500.
Volume
2
Issue
5
First Page
487
Last Page
500
ISSN
2326-6074
PMID
24795361
Abstract
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.
Recommended Citation
Wu T,
Xu K,
Banchereau R,
Marches F,
Yu C,
Martinek J,
Anguiano E,
Pedroza-Gonzalez A,
Snipes G,
O'Shaughnessy J,
Nishimura S,
Liu Y,
Pascual V,
Banchereau J,
Oh S,
Palucka K.
Reprogramming Tumor-Infiltrating Dendritic Cells for CD103+CD8+ Mucosal T-cell Differentiation and Breast Cancer Rejection. Cancer Immunol Res 2014 May 2(5):487-500.