Targeted Stat2 deletion in conventional dendritic cells impairs CTL responses but does not affect antibody production

Connie C. Qiu, Kevin P. Kotredes, Tess Cremers, Sajan Patel, Alexandra Afanassiev, Michael Slifker, Stefania Gallucci, Ana M. Gamero

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

STAT2 is a central component of the ISGF3 transcriptional complex downstream of type I interferon (IFN-I) signaling. The significance of in vivo IFN-I/STAT1 signals in cDCs is well-established in the generation of antitumor cytotoxic T cell (CTL) responses. However, the role of STAT2 has remained elusive. Here, we report a clinical correlation between cDC markers and STAT2 associated with better survival in human metastatic melanoma. In a murine tumor transplantation model, targeted Stat2 deletion in CD11c+cDCs enhanced tumor growth unaffected by IFNβ therapy. Furthermore, STAT2 was essential for both, the activation of CD8a+cDCs and CD11b+cDCs and antigen cross-presentation in vivo for the generation of robust T cell killing response. In contrast, STAT2 in CD11c+cDCs was dispensable for stimulating an antigen-specific humoral response, which was impaired in global Stat2 deficient mice. Thus, our studies indicate that STAT2 in cDCs is critical in host IFN-I signals by sculpting CTL responses against tumors.

Original languageEnglish
Article number1860477
Pages (from-to)1860477
JournalOncoImmunology
Volume10
Issue number1
DOIs
StatePublished - 2021

Keywords

  • STAT2
  • T cell
  • dendritic cells
  • interferon
  • tumor

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