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Type I interferon activates MHC class I-dressed CD11b+ conventional dendritic cells to promote protective anti-tumor CD8+ T cell immunity.
Duong, Ellen; Fessenden, Tim B; Lutz, Emi; Dinter, Teresa; Yim, Leon; Blatt, Sarah; Bhutkar, Arjun; Wittrup, Karl Dane; Spranger, Stefani.
Afiliação
  • Duong E; Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA, USA; Department of Biology, MIT, Cambridge, MA, USA.
  • Fessenden TB; Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA, USA.
  • Lutz E; Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA, USA; Department of Biological Engineering, MIT, Cambridge, MA, USA.
  • Dinter T; Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA, USA; Department of Biology, MIT, Cambridge, MA, USA.
  • Yim L; Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA, USA.
  • Blatt S; Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA, USA.
  • Bhutkar A; Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA, USA.
  • Wittrup KD; Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA, USA; Department of Biological Engineering, MIT, Cambridge, MA, USA.
  • Spranger S; Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA, USA; Department of Biology, MIT, Cambridge, MA, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA. Electronic address: spranger@mit.edu.
Immunity ; 55(2): 308-323.e9, 2022 02 08.
Article em En | MEDLINE | ID: mdl-34800368
ABSTRACT
Tumor-infiltrating dendritic cells (DCs) assume varied functional states that impact anti-tumor immunity. To delineate the DC states associated with productive anti-tumor T cell immunity, we compared spontaneously regressing and progressing tumors. Tumor-reactive CD8+ T cell responses in Batf3-/- mice lacking type 1 DCs (DC1s) were lost in progressor tumors but preserved in regressor tumors. Transcriptional profiling of intra-tumoral DCs within regressor tumors revealed an activation state of CD11b+ conventional DCs (DC2s) characterized by expression of interferon (IFN)-stimulated genes (ISGs) (ISG+ DCs). ISG+ DC-activated CD8+ T cells ex vivo comparably to DC1. Unlike cross-presenting DC1, ISG+ DCs acquired and presented intact tumor-derived peptide-major histocompatibility complex class I (MHC class I) complexes. Constitutive type I IFN production by regressor tumors drove the ISG+ DC state, and activation of MHC class I-dressed ISG+ DCs by exogenous IFN-ß rescued anti-tumor immunity against progressor tumors in Batf3-/- mice. The ISG+ DC gene signature is detectable in human tumors. Engaging this functional DC state may present an approach for the treatment of human disease.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Dendríticas / Antígenos de Histocompatibilidade Classe I / Interferon Tipo I / Linfócitos do Interstício Tumoral / Linfócitos T CD8-Positivos Limite: Animals Idioma: En Revista: Immunity Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Dendríticas / Antígenos de Histocompatibilidade Classe I / Interferon Tipo I / Linfócitos do Interstício Tumoral / Linfócitos T CD8-Positivos Limite: Animals Idioma: En Revista: Immunity Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos