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Vesicular stomatitis virus sensitizes immunologically cold tumors to checkpoint blockade by inducing pyroptosis.
Lin, Jing; Liu, Fei; Gao, Fei; Chen, Yujia; Wang, Renling; Wang, Xinyue; Li, Yue; Li, Qi; Sun, Shihui; Li, Zi; Lan, Yungang; Lu, Huijun; Guo, Wei; Du, Li; Gao, Feng; Song, Deguang; Zhao, Kui; Guan, Jiyu; He, Wenqi.
Afiliación
  • Lin J; State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China.
  • Liu F; State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China.
  • Gao F; Department of Laboratory Animals, College of Animal Science, Jilin University, 130062 Changchun, China.
  • Chen Y; Department of Gastrointestinal Surgery, The First Hospital of Jilin University, 130021 Changchun, China.
  • Wang R; State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China.
  • Wang X; State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China.
  • Li Y; State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China.
  • Li Q; State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China.
  • Sun S; State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China.
  • Li Z; State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China.
  • Lan Y; State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China.
  • Lu H; State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China.
  • Guo W; Department of Hematology, The first hospital of Jilin University, 130021 Changchun, China.
  • Du L; Department of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, 130041 Changchun, Jilin, China.
  • Gao F; State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China.
  • Song D; State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China.
  • Zhao K; State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China. Electronic address: kuizhao@jlu.edu.cn.
  • Guan J; State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China. Electronic address: jiygua@jlu.edu.cn.
  • He W; State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China. Electronic address: hewq@jlu.edu.cn.
Biochim Biophys Acta Mol Basis Dis ; 1868(12): 166538, 2022 12 01.
Article en En | MEDLINE | ID: mdl-36096276
BACKGROUND: Traditionally, vesicular stomatitis virus (VSV) and other oncolytic viruses (OVs) are thought to kill tumors by inducing apoptosis. However, cell apoptosis leads to immune quiescence, which is incompatible with the ability of OVs to activate the antitumor immune microenvironment. Thus, studying OVs-mediated oncolytic mechanisms is of great importance for the clinical application of OVs. METHODS: We examined the pyroptosis in tumor cells and tissues by morphological observation, Lactate Dehydrogenase (LDH) assay, frozen section observation, and western-blotting techniques. The critical role of GSDME in VSV-induced pyroptosis was confirmed by CRISPR/Cas9 technique. VSV virotherapy-recruited cytotoxic lymphocytes in the tumors were examined by flow cytometry assay. VSV-activated antitumor immunity was further enhanced by the co-administration with anti-PD-1 antibody. RESULTS: Here, we observed that VSV was able to trigger tumor pyroptosis through Gasdermin E (GSDME) in tumor cells, human tumor samples, and tumor-bearing mouse models. Importantly, the effectiveness of VSV-based virotherapy is highly dependent on GSDME, as depletion of GSDME not only reverses VSV-induced tumor-suppressive effects but also diminishes the ability of VSV to activate antitumor immunity. Notably, VSV treatment makes immunologically 'cold' tumors more sensitive to checkpoint blockade. CONCLUSIONS: Oncolytic VSV induces tumor cell pyroptosis by activating GSDME. GSDME is critical in recruiting cytotoxic T lymphocytes in the context of VSV therapy, which can switch immunologically 'cold' tumors into 'hot' and enhance immune checkpoint therapy efficacy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Virus Oncolíticos / Estomatitis Vesicular / Neoplasias Límite: Animals / Humans Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Virus Oncolíticos / Estomatitis Vesicular / Neoplasias Límite: Animals / Humans Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos