Oncogenic KIT modulates type I interferon-mediated antitumor immunity in GIST
Menée à l'aide de lignées cellulaires, d'échantillons tumoraux et de modèles murins de tumeur stromale gastro-intestinale, cette étude met en évidence un mécanisme par lequel l'oncogène KIT réduit l'immunité antitumorale induite par l'interféron de type I
Type I interferons (IFN) are implicated in tumor immunogenicity and response to systemic therapy, but their interaction with oncogene signaling is not well understood. Here, we studied oncogenic KIT, which drives gastrointestinal stromal tumor (GIST), the most common sarcoma. Using mouse models of GIST, we found that KIT inhibition reduced type I IFN production and signaling, which downregulated tumor MHC class I expression. Absence of type I IFN signaling increased tumor size, in part due to CD8+ T-cell impairment. Oncogenic KIT was required for GIST type I IFN signal transduction via STAT1. In human GIST cell lines and surgical specimens, type I IFN signaling contributed to HLA class I expression and correlated with tumor immunogenicity. Augmenting the type I IFN response partially compensated for the immunosuppressive effects of KIT inhibition. Thus, KIT signaling contributes to type I IFN signaling while KIT inhibition attenuates tumor immunogenicity and is party rescued by innate immune stimulation.