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Host STAT2/type I interferon axis controls tumor growth
Author(s) -
Yue Chanyu,
Xu Jun,
Tan Estioko Marc Daryl,
Kotredes Kevin P.,
LopezOtalora Yolanda,
Hilliard Brendan A.,
Baker Darren P.,
Gallucci Stefania,
Gamero Ana M.
Publication year - 2014
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.29004
Subject(s) - stat2 , cd8 , cancer research , cross presentation , interferon , immunotherapy , adoptive cell transfer , biology , melanoma , antigen , antigen presentation , immune system , immunology , t cell , microbiology and biotechnology , signal transduction , stat , stat3
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.