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Critical Role for CD103(+)/CD141(+) Dendritic Cells Bearing CCR7 for Tumor Antigen Trafficking and Priming of T Cell Immunity in Melanoma.
Roberts, Edward W; Broz, Miranda L; Binnewies, Mikhail; Headley, Mark B; Nelson, Amanda E; Wolf, Denise M; Kaisho, Tsuneyasu; Bogunovic, Dusan; Bhardwaj, Nina; Krummel, Matthew F.
Afiliação
  • Roberts EW; Department of Pathology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0511, USA.
  • Broz ML; Department of Pathology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0511, USA.
  • Binnewies M; Department of Pathology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0511, USA.
  • Headley MB; Department of Pathology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0511, USA.
  • Nelson AE; Department of Pathology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0511, USA.
  • Wolf DM; Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA 94143, USA.
  • Kaisho T; Institute of Advanced Medicine, Wakayama Medical University, Wakayama 641-8509, Japan.
  • Bogunovic D; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Bhardwaj N; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Krummel MF; Department of Pathology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0511, USA. Electronic address: matthew.krummel@ucsf.edu.
Cancer Cell ; 30(2): 324-336, 2016 08 08.
Article em En | MEDLINE | ID: mdl-27424807
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Dendríticas / Linfócitos T CD8-Positivos / Receptores CCR7 / Melanoma Limite: Animals / Humans Idioma: En Revista: Cancer Cell Assunto da revista: NEOPLASIAS Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Dendríticas / Linfócitos T CD8-Positivos / Receptores CCR7 / Melanoma Limite: Animals / Humans Idioma: En Revista: Cancer Cell Assunto da revista: NEOPLASIAS Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos