TY - JOUR T1 - Autophagy induction by thiostrepton improves the efficacy of immunogenic chemotherapy JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1136/jitc-2019-000462 VL - 8 IS - 1 SP - e000462 AU - Yan Wang AU - Wei Xie AU - Juliette Humeau AU - Guo Chen AU - Peng Liu AU - Jonathan Pol AU - Zhen Zhang AU - Oliver Kepp AU - Guido Kroemer Y1 - 2020/03/01 UR - http://jitc.bmj.com/content/8/1/e000462.abstract N2 - Background Immunogenic cell death (ICD) is a peculiar modality of cellular demise that elicits adaptive immune responses and triggers T cell-dependent immunity.Methods Fluorescent biosensors were employed for an unbiased drug screen approach aiming at the identification of ICD enhancers.Results Here, we discovered thiostrepton as an enhancer of ICD able to boost chemotherapy-induced ATP release, calreticulin exposure and high-mobility group box 1 exodus. Moreover, thiostrepton enhanced anticancer immune responses of oxaliplatin (OXA) in vivo in immunocompetent mice, yet failed to do so in immunodeficient animals. Consistently, thiostrepton combined with OXA altered the ratio of cytotoxic T lymphocytes to regulatory T cells, thus overcoming immunosuppression and reinstating anticancer immunosurveillance.Conclusion Altogether, these results indicate that thiostrepton can be advantageously combined with chemotherapy to enhance anticancer immunogenicity. ER -