Medium dose intermittent cyclophosphamide induces immunogenic cell death and cancer cell autonomous type I interferon production in glioma models.

ABSTRACT: Cyclophosphamide treatment on a medium-dose, intermittent chemotherapy (MEDIC) schedule activates both innate and adaptive immunity leading to major regression of implanted gliomas. Here, we show that this MEDIC treatment regimen induces tumor cell autonomous type-I interferon signaling, followed by release of soluble factors that activate interferon-stimulated genes in both tumor cells and tumor-infiltrating immune cells. In cultured GL261 and CT-2A glioma cells, activated cyclophosphamide stimulated production and release of type-I interferons, leading to robust activation of downstream gene targets. Antibody against the type-I interferon receptor IFNAR1 blocked the cyclophosphamide-stimulated induction of these genes in both cultured glioma cells and implanted gliomas. Furthermore, IFNA

SUBMITTER: Du B 

PROVIDER: S-EPMC6956245 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature