title: Reprogramming tumor-infiltrating dendritic cells for CD103+ CD8+ mucosal T-cell differentiation and breast cancer rejection.
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.
authors.affiliation: Authors' Affiliations: Department of Oncological Sciences, Mount Sinai School of Medicine, New York, New York.
authors.forename: Te-Chia
authors.initials: TC
authors.lastname: Wu
authors.forename: Kangling
authors.initials: K
authors.lastname: Xu
authors.forename: Romain
authors.initials: R
authors.lastname: Banchereau
authors.forename: Florentina
authors.initials: F
authors.lastname: Marches
authors.forename: Chun I
authors.initials: CI
authors.lastname: Yu
authors.forename: Jan
authors.initials: J
authors.lastname: Martinek
authors.forename: Esperanza
authors.initials: E
authors.lastname: Anguiano
authors.forename: Alexander
authors.initials: A
authors.lastname: Pedroza-Gonzalez
authors.forename: G Jackson
authors.initials: GJ
authors.lastname: Snipes
authors.forename: Joyce
authors.initials: J
authors.lastname: O'Shaughnessy
authors.forename: Stephen
authors.initials: S
authors.lastname: Nishimura
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
authors.forename: Virginia
authors.initials: V
authors.lastname: Pascual
authors.forename: Jacques
authors.initials: J
authors.lastname: Banchereau
authors.forename: Sangkon
authors.initials: S
authors.lastname: Oh
authors.forename: Karolina
authors.initials: K
authors.lastname: Palucka
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism; D051379:Mice; D009092:Mucous Membrane / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D047071:beta-Glucans / Q000276:immunology / Q000494:pharmacology; D000099181:Dectin-1
chemical_list: D037181:Lectins, C-Type; D016212:Transforming Growth Factor beta; D047071:beta-Glucans; D000099181:Dectin-1; C038459:curdlan