Manipulating mitochondrial electron flow enhances tumor immunogenicity.
In: The Scientific monthly, Jg. 381 (2023-09-22), Heft 6664
Online
academicJournal
Although tumor growth requires the mitochondrial electron transport chain (ETC), the relative contribution of complex I (CI) and complex II (CII), the gatekeepers for initiating electron flow, remains unclear. In this work, we report that the loss of CII, but not that of CI, reduces melanoma tumor growth by increasing antigen presentation and T cell-mediated killing. This is driven by succinate-mediated transcriptional and epigenetic activation of major histocompatibility complex-antigen processing and presentation (MHC-APP) genes independent of interferon signaling. Furthermore, knockout of methylation-controlled J protein (MCJ), to promote electron entry preferentially through CI, provides proof of concept of ETC rewiring to achieve antitumor responses without side effects associated with an overall reduction in mitochondrial respiration in noncancer cells. Our results may hold therapeutic potential for tumors that have reduced MHC-APP expression, a common mechanism of cancer immunoevasion.
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Manipulating mitochondrial electron flow enhances tumor immunogenicity.
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Autor/in / Beteiligte Person: | Mangalhara, Kailash ; Varanasi, Siva ; Johnson, Melissa ; Burns, Mannix ; Rojas, Gladys ; Esparza Moltó, Pau ; Sainz, Alva ; Tadepalle, Nimesha ; Abbott, Keene ; Mendiratta, Gaurav ; Chen, Dan ; Farsakoglu, Yagmur ; Kunchok, Tenzin ; Hoffmann, Filipe ; Parisi, Bianca ; Rincon, Mercedes ; Vander Heiden, Matthew ; Bosenberg, Marcus ; Kaech, Susan ; Shadel, Gerald ; Hargreaves, Diana |
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Zeitschrift: | The Scientific monthly, Jg. 381 (2023-09-22), Heft 6664 |
Veröffentlichung: | eScholarship, University of California, 2023 |
Medientyp: | academicJournal |
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