TY - JOUR
T1 - Reprogramming tumor-infiltrating dendritic cells for CD103+CD8+ Mucosal T-cell differentiation and breast cancer rejection
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
N1 - Publisher Copyright:
© 2014 American Association for Cancer Research.
PY - 2014/5
Y1 - 2014/5
N2 - 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 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 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:C, induce CD8+ T cells to express CD13 (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.
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 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 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:C, induce CD8+ T cells to express CD13 (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.
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U2 - 10.1158/2326-6066.CIR-13-0217
DO - 10.1158/2326-6066.CIR-13-0217
M3 - Article
C2 - 24795361
AN - SCOPUS:84905820953
SN - 2326-6066
VL - 2
SP - 487
EP - 500
JO - Cancer Immunology Research
JF - Cancer Immunology Research
IS - 5
ER -