Journal
ONCOIMMUNOLOGY
Volume 10, Issue 1, Pages -Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2020.1860477
Keywords
STAT2; dendritic cells; T cell; interferon; tumor
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Funding
- Temple University Bridge Funds [R03 CA215929, R21AI119947, P30 CA006927]
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STAT2 in cDCs plays a critical role in sculpting host IFN-I signals by activating CD8a+cDCs and CD11b+cDCs, as well as promoting antigen cross-presentation in vivo, leading to a robust T cell killing response against tumors.
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 IFN beta 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.
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