The pursuit of innovative therapeutic strategies in oncology remains imperative, given the persistent global impact of cancer as a leading cause of mortality. Immunotherapy is regarded as one of the most promising techniques for systemic cancer therapies among the several therapeutic options available. Nevertheless, limited immune response rates and immune resistance urge us on an augmentation for therapeutic efficacy rather than sticking to conventional approaches. Ferroptosis, a novel reprogrammed cell death, is tightly correlated with the tumor immune environment and interferes with cancer progression. Highly mutant or metastasis-prone tumor cells are more susceptible to iron-dependent nonapoptotic cell death. Consequently, ferroptosis-induction therapies hold the promise of overcoming resistance to conventional treatments. The most prevalent post-transcriptional modification, RNA m6A modification, regulates the metabolic processes of targeted RNAs and is involved in numerous physiological and pathological processes. Aberrant m6A modification influences cell susceptibility to ferroptosis, as well as the expression of immune checkpoints. Clarifying the regulation of m6A modification on ferroptosis and its significance in tumor cell response will provide a distinct method for finding potential targets to enhance the effectiveness of immunotherapy. In this review, we comprehensively summarized regulatory characteristics of RNA m6A modification on ferroptosis and discussed the role of RNA m6A-mediated ferroptosis on immunotherapy, aiming to enhance the effectiveness of ferroptosis-sensitive immunotherapy as a treatment for immune-resistant malignancies.

中文翻译：

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铁死亡中 RNA m6A 修饰：对推进肿瘤免疫治疗的影响


鉴于癌症作为主要死亡原因的持续全球影响，寻求肿瘤学创新治疗策略仍然势在必行。免疫疗法被认为是可用的几种治疗方案中最有前途的全身性癌症治疗技术之一。然而，有限的免疫反应率和免疫抵抗力促使我们提高治疗效果，而不是坚持传统方法。Ferroptosis（铁死亡）是一种新型的重程序性细胞死亡，与肿瘤免疫环境密切相关，并干扰癌症进展。高度突变或易转移的肿瘤细胞更容易发生铁依赖性非凋亡细胞死亡。因此，铁死亡诱导疗法有望克服对常规治疗的耐药性。最普遍的转录后修饰 RNA m6A 修饰调节靶向 RNA 的代谢过程，并参与许多生理和病理过程。异常的 m6A 修饰会影响细胞对铁死亡的易感性以及免疫检查点的表达。阐明 m6A 修饰对铁死亡的调节及其在肿瘤细胞反应中的意义将为寻找潜在靶点以增强免疫治疗的有效性提供一种独特的方法。本文全面总结了 RNA m6A 修饰对铁死亡的调控特性，并讨论了 RNA m6A 介导的铁死亡对免疫治疗的作用，旨在提高铁死亡敏感免疫治疗免疫治疗免疫耐药恶性肿瘤的有效性。