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Unleashing Type-2 Dendritic Cells to Drive Protective Antitumor CD4+ T Cell Immunity.
Binnewies, Mikhail; Mujal, Adriana M; Pollack, Joshua L; Combes, Alexis J; Hardison, Emily A; Barry, Kevin C; Tsui, Jessica; Ruhland, Megan K; Kersten, Kelly; Abushawish, Marwan A; Spasic, Marko; Giurintano, Jonathan P; Chan, Vincent; Daud, Adil I; Ha, Patrick; Ye, Chun J; Roberts, Edward W; Krummel, Matthew F.
Afiliación
  • Binnewies M; Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Mujal AM; Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Pollack JL; Pionyr Immunotherapeutics, San Francisco, CA 94080, USA.
  • Combes AJ; Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA; UCSF Immunoprofiler Initiative, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Hardison EA; Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Barry KC; Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA; UCSF Immunoprofiler Initiative, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Tsui J; Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA; UCSF Immunoprofiler Initiative, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Ruhland MK; Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Kersten K; Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Abushawish MA; Pionyr Immunotherapeutics, San Francisco, CA 94080, USA.
  • Spasic M; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Giurintano JP; Department of Otolaryngology-Head and Neck Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Chan V; Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA; UCSF Immunoprofiler Initiative, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Daud AI; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Ha P; Department of Otolaryngology-Head and Neck Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Ye CJ; Institute of Human Genetics, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Roberts EW; Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Krummel MF; Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA; UCSF Immunoprofiler Initiative, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: matthew.krummel@ucsf.edu.
Cell ; 177(3): 556-571.e16, 2019 04 18.
Article en En | MEDLINE | ID: mdl-30955881
Differentiation of proinflammatory CD4+ conventional T cells (Tconv) is critical for productive antitumor responses yet their elicitation remains poorly understood. We comprehensively characterized myeloid cells in tumor draining lymph nodes (tdLN) of mice and identified two subsets of conventional type-2 dendritic cells (cDC2) that traffic from tumor to tdLN and present tumor-derived antigens to CD4+ Tconv, but then fail to support antitumor CD4+ Tconv differentiation. Regulatory T cell (Treg) depletion enhanced their capacity to elicit strong CD4+ Tconv responses and ensuing antitumor protection. Analogous cDC2 populations were identified in patients, and as in mice, their abundance relative to Treg predicts protective ICOS+ PD-1lo CD4+ Tconv phenotypes and survival. Further, in melanoma patients with low Treg abundance, intratumoral cDC2 density alone correlates with abundant CD4+ Tconv and with responsiveness to anti-PD-1 therapy. Together, this highlights a pathway that restrains cDC2 and whose reversal enhances CD4+ Tconv abundance and controls tumor growth.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Células Dendríticas / Linfocitos T CD4-Positivos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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PubMed Links
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Células Dendríticas / Linfocitos T CD4-Positivos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos