Type I interferon suppresses tumor growth through activating the STAT3-granzyme B pathway in tumor-infiltrating cytotoxic T lymphocytes

摘要: Type I interferons (IFN-I) have recently emerged as key regulators of tumor response to chemotherapy and immunotherapy. However, IFN-I function in cytotoxic T lymphocytes (CTLs) the microenvironment is largely unknown. Tumor tissues CTLs human colorectal cancer patients were analyzed for interferon (alpha beta) receptor 1 (IFNAR1) expression. IFNAR1 knock out (IFNAR-KO), mixed wild type (WT) IFNAR1-KO bone marrow chimera mice, mice with deficiency only cells (IFNAR1-TKO) used determine suppression. target genes tumor-infiltrating antigen-specific identified functionally analyzed. expression level significantly lower carcinoma tissue than normal colon tissue. protein also on from those healthy donors. Although exhibited increased susceptibility methylcholanthrene-induced sarcoma, IFNAR1-sufficient tumors grow faster (IFNAR1-TKO), suggesting that functions enhance host immunosurveillance. Strikingly, CTL levels are similar between tumor-bearing WT mice. Competitive reconstitution further determined IFNAR1-deficient naive exhibit no vaccination generate compared CTLs. Gene profiling Gzmb down-regulated vivo. Mechanistically, we activates STAT3 binds promoter activate transcription induces activation effector suppress development. Human may use down-regulation evade