Journal
JOURNAL FOR IMMUNOTHERAPY OF CANCER
Volume 8, Issue 1, Pages -Publisher
BMJ PUBLISHING GROUP
DOI: 10.1136/jitc-2019-000462
Keywords
adaptive immunity; immunomodulation
Categories
Funding
- China Scholarship Council
- National Nature Science Foundation of China [81502049, 81572955, 81773357]
- Ligue contre le Cancer
- Agence National de la Recherche (ANR)
- ANR
- ERA-Net for Research on Rare Diseases
- AMMICa US23/CNRS [UMS3655]
- Association pour la recherche sur le cancer (ARC)
- Association Le Cancer du Sein, Parlons-en!
- Canceropole Ile-de-France
- Chancelerie des universites de Paris (Legs Poix)
- Fondation pour la Recherche Medicale (FRM)
- European Research Area Network on Cardiovascular Diseases (ERA-CVD, MINOTAUR)
- Gustave Roussy Odyssea
- European Union Horizon 2020 Project Oncobiome
- Fondation Carrefour
- High-end Foreign Expert Program in China [GDW20171100085]
- Institut National du Cancer (INCa)
- Inserm (HTE)
- Institut Universitaire de France
- LeDucq Foundation
- LabEx Immuno-Oncology [ANR-18-IDEX-0001]
- RHU Torino Lumiere
- Seerave Foundation
- SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE)
- SIRIC Cancer Research and Personalized Medicine (CARPEM)
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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.
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