title: Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity.
abstract: It is well understood that antigen-presenting cells (APCs) within tumors typically do not maintain cytotoxic T cell (CTL) function, despite engaging them. Across multiple mouse tumor models and human tumor biopsies, we have delineated the intratumoral dendritic cell (DC) populations as distinct from macrophage populations. Within these, CD103(+) DCs are extremely sparse and yet remarkably capable CTL stimulators. These are uniquely dependent on IRF8, Zbtb46, and Batf3 transcription factors and are generated by GM-CSF and FLT3L cytokines. Regressing tumors have higher proportions of these cells, T-cell-dependent immune clearance relies on them, and abundance of their transcripts in human tumors correlates with clinical outcome. This cell type presents opportunities for prognostic and therapeutic approaches across multiple cancer types.
authors.affiliation: Department of Pathology, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Miranda L
authors.initials: ML
authors.lastname: Broz
authors.affiliation: Department of Pathology, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Binnewies
authors.affiliation: Department of Pathology, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Bijan
authors.initials: B
authors.lastname: Boldajipour
authors.affiliation: Department of Pathology, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Nelson
authors.affiliation: Lung Biology Center, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Pollack
authors.affiliation: Lung Biology Center, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Erle
authors.affiliation: Lung Biology Center, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Barczak
authors.affiliation: Department of Dermatology, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Rosenblum
authors.affiliation: Melanoma Clinical Research Unit, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Adil
authors.initials: A
authors.lastname: Daud
authors.affiliation: Department of Cell and Tissue Biology, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Diane L
authors.initials: DL
authors.lastname: Barber
authors.affiliation: INSERM U932, Immunity and Cancer, Institut Curie, 75248 Paris Cedex 05, France.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Amigorena
authors.affiliation: Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Van't Veer
authors.affiliation: Committee on Immunology, University of Chicago, 924 E. 57th Street, Chicago, IL 60637, USA.
authors.forename: Anne I
authors.initials: AI
authors.lastname: Sperling
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: Department of Pathology, University of California San Francisco, San Francisco, CA 94143, USA. Electronic address: matthew.krummel@ucsf.edu.
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Krummel
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D008264:Macrophages / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment
chemical_list: D015703:Antigens, CD