RT Journal Article
SR Electronic
T1 Autophagy induction by thiostrepton improves the efficacy of immunogenic chemotherapy
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP e000462
DO 10.1136/jitc-2019-000462
VO 8
IS 1
A1 Wang, Yan
A1 Xie, Wei
A1 Humeau, Juliette
A1 Chen, Guo
A1 Liu, Peng
A1 Pol, Jonathan
A1 Zhang, Zhen
A1 Kepp, Oliver
A1 Kroemer, Guido
YR 2020
UL http://jitc.bmj.com/content/8/1/e000462.abstract
AB 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.