T细胞浸润低、针对肿瘤的T细胞活性无效以及肿瘤抗原呈递减少会促进肿瘤逃避免疫。 TET2 DNA 双加氧酶基因在造血系统恶性肿瘤中经常发生突变，并且在多种实体瘤中发现 TET 酶活性丧失。我们之前表明，TET2 的辅助因子维生素 C (VC) 以 TET2 依赖性方式增强肿瘤相关 T 细胞募集和检查点抑制剂治疗反应。通过对 B16-OVA 黑色素瘤肿瘤进行单细胞 RNA 测序 (scRNA-seq) 分析，我们发现 TET2 在肿瘤中的另一个功能是促进某些抗原呈递机制基因的表达，而 VC 可以有效增强这种功能。一致地，VC 以 TET2 依赖性方式促进基于细胞和肿瘤测定的抗原呈递。对 scRNA-seq 数据集的细胞间信号传导进行量化表明，肿瘤和肿瘤微环境内 T 细胞衍生的 IFNγ 诱导的信号传导需要肿瘤相关的 TET2 表达，而 VC 治疗会增强这种表达。对患者肿瘤样本的分析表明，TET 活性与抗原呈递基因表达和患者结果直接相关。我们的结果证明了肿瘤相关 TET2 活性作为肿瘤免疫的关键介质的重要性，高剂量 VC 治疗可增强肿瘤免疫的作用。

Immune evasion by tumors is promoted by low T cell infiltration, ineffective T cell activity directed against the tumor and reduced tumor antigen presentation. The TET2 DNA dioxygenase gene is frequently mutated in hematopoietic malignancies and loss of TET enzymatic activity is found in a variety of solid tumors. We showed previously that vitamin C (VC), a co-factor of TET2, enhances tumor-associated T cell recruitment and checkpoint inhibitor therapy responses in a TET2-dependent manner. Using single-cell RNA sequencing (scRNA-seq) analysis performed on B16-OVA melanoma tumors, we have shown here that an additional function for TET2 in tumors is to promote expression of certain antigen presentation machinery genes, which is potently enhanced by VC. Consistently, VC promoted antigen presentation in cell-based and tumor assays in a TET2-dependent manner. Quantifying intercellular signaling from the scRNA-seq dataset showed that T cell-derived IFNγ-induced signaling within the tumor and tumor microenvironment requires tumor-associated TET2 expression which is enhanced by VC treatment. Analysis of patient tumor samples indicated that TET activity directly correlates with antigen-presentation gene expression and with patient outcomes. Our results demonstrate the importance of tumor-associated TET2 activity as a critical mediator of tumor immunity which is augmented by high-dose VC therapy.