Work

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

Year: 2020

Type: article

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.

Source: OncoImmunology

DOI: 10.1080/2162402x.2020.1860477