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oai:repisalud.isciii.es:20.500.12105/137152024-09-27T09:06:23Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Prota, Gennaro author Gileadi, Uzi author Rei, Margarida author Lechuga-Vieco, Ana Victoria author Chen, Ji-Li author Galiani, Silvia author Bedard, Melissa author Lau, Vivian Wing Chong author Fanchi, Lorenzo F author Artibani, Mara author Hu, Zhiyuan author Gordon, Siamon author Rehwinkel, Jan author Enriquez, Jose Antonio author Ahmed, Ahmed A author Schumacher, Ton N author Cerundolo, Vincenzo author 2020-05 Epitopes derived from mutated cancer proteins elicit strong antitumor T-cell responses that correlate with clinical efficacy in a proportion of patients. However, it remains unclear whether the subcellular localization of mutated proteins influences the efficiency of T-cell priming. To address this question, we compared the immunogenicity of NY-ESO-1 and OVA localized either in the cytosol or in mitochondria. We showed that tumors expressing mitochondrial-localized NY-ESO-1 and OVA proteins elicit significantdly higher frequencies of antigen-specific CD8+ T cells in vivo. We also demonstrated that this stronger immune response is dependent on the mitochondrial location of the antigenic proteins, which contributes to their higher steady-state amount, compared with cytosolic localized proteins. Consistent with these findings, we showed that injection of mitochondria purified from B16 melanoma cells can protect mice from a challenge with B16 cells, but not with irrelevant tumors. Finally, we extended these findings to cancer patients by demonstrating the presence of T-cell responses specific for mutated mitochondrial-localized proteins. These findings highlight the utility of prioritizing epitopes derived from mitochondrial-localized mutated proteins as targets for cancer vaccination strategies. Cancer Immunol Res. 2020; 8(5):685-697 10.1158/2326-6066.CIR-19-0467 2326-6074 Cancer immunology research 32205315 http://hdl.handle.net/20.500.12105/13715 Enhanced Immunogenicity of Mitochondrial-Localized Proteins in Cancer Cells.