Mitochondrial metabolism and electron transport chain (ETC) function are essential for tumour proliferation and metastasis. However, the impact of ETC function on cancer immunogenicity is not well understood. In a recent study, Mangalhara et al. found that inhibition of complex II leads to enhanced tumour immunogenicity, T-cell-mediated cytotoxicity and inhibition of tumour growth. Surprisingly, this antitumour effect is mediated by succinate accumulation affecting histone methylation. Histone methylation promotes the transcriptional upregulation of major histocompatibility complex–antigen processing and presentation (MHC-APP) genes in a manner independent of interferon signalling. Modulating mitochondrial electron flow to enhance tumour immunogenicity provides an exciting new therapeutic avenue and may be particularly attractive for tumours with reduced expression of MHC-APP genes or dampened interferon signalling.

中文翻译：

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肿瘤免疫原性与（线粒体电子）流有关

线粒体代谢和电子传递链（ETC）功能对于肿瘤增殖和转移至关重要。然而，ETC 功能对癌症免疫原性的影响尚不清楚。在最近的一项研究中，Mangalhara 等人。发现抑制复合物 II 会增强肿瘤免疫原性、T 细胞介导的细胞毒性并抑制肿瘤生长。令人惊讶的是，这种抗肿瘤作用是由影响组蛋白甲基化的琥珀酸积累介导的。组蛋白甲基化以独立于干扰素信号传导的方式促进主要组织相容性复合物-抗原加工和呈递（MHC-APP）基因的转录上调。调节线粒体电子流以增强肿瘤免疫原性提供了一种令人兴奋的新治疗途径，并且对于 MHC-APP 基因表达减少或干扰素信号传导减弱的肿瘤可能特别有吸引力。