TMEM87A suppresses ferroptosis and increases cancer immunotherapy resistance by maintaining the Golgi apparatus pH homeostasis

Researchers publishing in Nature Cancer have identified the protein TMEM87A as a key regulator of Golgi apparatus pH homeostasis that protects cancer cells from ferroptosis, a form of iron-dependent cell death driven by lipid peroxidation. The study by Li et al. demonstrates that TMEM87A counteracts ferroptosis-induced lipid peroxidation in the Golgi, and that its presence in tumors contributes to resistance against immune checkpoint immunotherapy. Critically, genetic ablation of TMEM87A sensitized multiple cancer types to ferroptosis, boosted antitumor immune responses, and improved the efficacy of immunotherapy in preclinical models. The findings point to TMEM87A as a potential therapeutic target whose inhibition could overcome immunotherapy resistance across a range of cancers. While the work remains preclinical, it opens a novel mechanistic avenue linking organelle pH regulation to tumor immune evasion.