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

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

Oncoimmunology (2021-01-19)
Connie C Qiu, Kevin P Kotredes, Tess Cremers, Sajan Patel, Alexandra Afanassiev, Michael Slifker, Stefania Gallucci, Ana M Gamero
ZUSAMMENFASSUNG

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.

MATERIALIEN
Produktnummer
Marke
Produktbeschreibung

Sigma-Aldrich
Anti-STAT2-Antikörper, Upstate®, from rabbit