title: Critical Role for CD103(+)/CD141(+) Dendritic Cells Bearing CCR7 for Tumor Antigen Trafficking and Priming of T Cell Immunity in Melanoma.
abstract: Intratumoral dendritic cells (DC) bearing CD103 in mice or CD141 in humans drive intratumoral CD8(+) T cell activation. Using multiple strategies, we identified a critical role for these DC in trafficking tumor antigen to lymph nodes (LN), resulting in both direct CD8(+) T cell stimulation and antigen hand-off to resident myeloid cells. These effects all required CCR7. Live imaging demonstrated direct presentation to T cells in LN, and CCR7 loss specifically in these cells resulted in defective LN T cell priming and increased tumor outgrowth. CCR7 expression levels in human tumors correlate with signatures of CD141(+) DC, intratumoral T cells, and better clinical outcomes. This work identifies an ongoing pathway to T cell priming, which should be harnessed for tumor therapies.
authors.affiliation: Department of Pathology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0511, USA.
authors.forename: Edward W
authors.initials: EW
authors.lastname: Roberts
authors.affiliation: Department of Pathology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0511, USA.
authors.forename: Miranda L
authors.initials: ML
authors.lastname: Broz
authors.affiliation: Department of Pathology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0511, USA.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Binnewies
authors.affiliation: Department of Pathology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0511, USA.
authors.forename: Mark B
authors.initials: MB
authors.lastname: Headley
authors.affiliation: Department of Pathology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0511, USA.
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Nelson
authors.affiliation: Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Denise M
authors.initials: DM
authors.lastname: Wolf
authors.affiliation: Institute of Advanced Medicine, Wakayama Medical University, Wakayama 641-8509, Japan.
authors.forename: Tsuneyasu
authors.initials: T
authors.lastname: Kaisho
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Dusan
authors.initials: D
authors.lastname: Bogunovic
authors.affiliation: Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Nina
authors.initials: N
authors.lastname: Bhardwaj
authors.affiliation: Department of Pathology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0511, USA. Electronic address: matthew.krummel@ucsf.edu.
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Krummel
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D006801:Humans; D039001:Integrin alpha Chains / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054400:Receptors, CCR7 / Q000276:immunology*; D018180:Thrombomodulin
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; C515370:CCR7 protein, human; C515371:Ccr7 protein, mouse; D039001:Integrin alpha Chains; D054400:Receptors, CCR7; C546931:THBD protein, human; D018180:Thrombomodulin; C091367:alpha E integrins
keywords: 2-photon imaging; anti-tumor T cell priming; antigen presentation; antigen trafficking; dendritic cells; draining lymph node; melanoma; tumor; tumor immune response