Host STAT2/type I interferon axis controls tumor growth

The role of STAT2 in mediating the antigrowth effects of type I interferon (IFN) is well‐documented in vitro . Yet evidence of IFN‐activated STAT2 as having tumor suppressor function in vivo and participation in antitumor immunity is lacking. Here we show in a syngeneic tumor transplantation model that STAT2 reduces tumor growth. Stat2 − / − mice formed larger tumors compared to wild type (WT) mice. IFN‐β treatment of Stat2 − / − mice did not cause tumor regression. Gene expression analysis revealed a small subset of immunomodulatory genes to be downregulated in tumors established in Stat2 − / − mice. Additionally, we found tumor antigen cross‐presentation by Stat2 − / − dendritic cells to T cells to be impaired. Adoptive transfer of tumor antigen specific CD8 + T cells primed by Stat2 − / − dendritic cells into tumor‐bearing Stat2 − / − mice did not induce tumor regression with IFN‐β intervention. We observed that an increase in the number of CD4 + and CD8 + T cells in the draining lymph nodes of IFN‐β‐treated tumor‐bearing WT mice was absent in IFN‐β treated Stat2 − / − mice. Thus our study provides evidence for further evaluation of STAT2 function in cancer patients receiving type I IFN based immunotherapy.