免疫疗法彻底改变了转移性黑色素瘤的治疗，但仍有大量患者没有反应，并且许多患者出现自身免疫不良事件。据报道，患者结果与单核细胞亚群之间存在关联，而维生素 C（抗坏血酸）已被证明可以在体外介导癌症刺激的单核细胞的变化。因此，我们研究了接受免疫治疗的转移性黑色素瘤患者中抗坏血酸与单核细胞亚群和表观遗传修饰的关系。将接受免疫治疗的患者与其他癌症队列和年龄匹配的健康对照进行比较。测量血浆和外周血单核细胞（PBMC）、单核细胞亚型和表观遗传标记物中的抗坏血酸水平，并记录不良事件、肿瘤反应和存活率。四分之一的免疫治疗队列患有维生素 C 缺乏症，血浆和 PBMC 抗坏血酸水平显着低于其他癌症患者或健康对照者。来自免疫治疗队列的 PBMC 包含相似频率的非经典和经典单核细胞。在健康对照中，DNA 甲基化标记和细胞内抗坏血酸浓度与单核细胞亚群频率相关，但在免疫治疗患者中则失去了相关性。抗坏血酸状态与免疫相关不良事件或肿瘤反应或总生存率之间没有明显的关联。

The treatment of metastatic melanoma has been revolutionised by immunotherapy, yet a significant number of patients do not respond, and many experience autoimmune adverse events. Associations have been reported between patient outcome and monocyte subsets, whereas vitamin C (ascorbate) has been shown to mediate changes in cancer-stimulated monocytes in vitro. We therefore investigated the relationship of ascorbate with monocyte subsets and epigenetic modifications in patients with metastatic melanoma receiving immunotherapy. Patients receiving immunotherapy were compared to other cancer cohorts and age-matched healthy controls. Ascorbate levels in plasma and peripheral blood-derived mononuclear cells (PBMCs), monocyte subtype and epigenetic markers were measured, and adverse events, tumour response and survival were recorded. A quarter of the immunotherapy cohort had hypovitaminosis C, with plasma and PBMC ascorbate levels significantly lower than those from other cancer patients or healthy controls. PBMCs from the immunotherapy cohort contained similar frequencies of non-classical and classical monocytes. DNA methylation markers and intracellular ascorbate concentration were correlated with monocyte subset frequency in healthy controls, but correlation was lost in immunotherapy patients. No associations between ascorbate status and immune-related adverse events or tumour response or overall survival were apparent.