Prevention of Tumor Growth and Dissemination by In Situ Vaccination with Mitochondria‐Targeted Atovaquone - Aix-Marseille Université Accéder directement au contenu
Article Dans Une Revue Advanced Science Année : 2022

Prevention of Tumor Growth and Dissemination by In Situ Vaccination with Mitochondria‐Targeted Atovaquone

Résumé

Atovaquone, an FDA-approved drug for malaria, is known to inhibit mitochondrial electron transport. A recently synthesized mitochondria-targeted atovaquone increased mitochondrial accumulation and antitumor activity in vitro. Using an in situ vaccination approach, local injection of mitochondria-targeted atovaquone into primary tumors triggered potent T cell immune responses locally and in distant tumor sites. Mitochondria-targeted atovaquone treatment led to significant reductions of both granulocytic myeloid-derived suppressor cells and regulatory T cells in the tumor microenvironment. Mitochondria-targeted atovaquone treatment blocks the expression of genes involved in oxidative phosphorylation and glycolysis in granulocytic-myeloid-derived suppressor cells and regulatory T cells, which may lead to death of granulocytic-myeloid-derived suppressor cells and regulatory T cells. Mitochondria-targeted atovaquone inhibits expression of genes for mitochondrial complex components, oxidative phosphorylation, and glycolysis in both granulocytic-myeloid-derived suppressor cells and regulatory T cells. The resulting decreases in intratumoral granulocytic-myeloid-derived suppressor cells and regulatory T cells could facilitate the observed increase in tumor-infiltrating CD4 + T cells. Mitochondria-targeted atovaquone also improves the anti-tumor activity of PD-1 blockade immunotherapy. The results implicate granulocytic-myeloid-derived suppressor cells and regulatory T cells as novel targets of mitochondria-targeted atovaquone that facilitate its antitumor efficacy.
Fichier principal
Vignette du fichier
mica7.pdf (9.18 Mo) Télécharger le fichier
Origine Publication financée par une institution
Licence

Dates et versions

hal-04115046 , version 1 (02-06-2023)

Licence

Identifiants

Citer

Mofei Huang, Donghai Xiong, Jing Pan, Qi Zhang, Yian Wang, et al.. Prevention of Tumor Growth and Dissemination by In Situ Vaccination with Mitochondria‐Targeted Atovaquone. Advanced Science, 2022, 9 (12), pp.2101267. ⟨10.1002/advs.202101267⟩. ⟨hal-04115046⟩
14 Consultations
11 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More