文章：

5-氮胞苷治疗使肿瘤细胞对t细胞介导的细胞毒性敏感，并调节髓系恶性肿瘤患者的NK细胞

5-Azacytidine treatment sensitizes tumor cells to T-cell mediated cytotoxicity and modulates NK cells in patients with myeloid malignancies

原文发布日期：2014-03-28

DOI: 10.1038/bcj.2014.14

类型: Original Article

开放获取: 是

英文摘要：

Treatment with the demethylating agent 5-Azacytidine leads to prolonged survival for patients with myelodysplastic syndrome, and the demethylation induces upregulation of cancer-testis antigens. Cancer-testis antigens are well-known targets for immune recognition in cancer, and the immune system may have a role in this treatment regimen. We show here that 5-Azacytidine treatment leads to increased T-cell recognition of tumor cells. T-cell responses against a large panel of cancer-testis antigens were detected before treatment, and these responses were further induced upon initiation of treatment. These characteristics point to an ideal combination of 5-Azacytidine and immune therapy to preferentially boost T-cell responses against cancer-testis antigens. To initiate such combination therapy, essential knowledge is required about the general immune modulatory effect of 5-Azacytidine. We therefore examined potential treatment effects on both immune stimulatory (CD8 and CD4 T cells and Natural Killer (NK) cells) and immune inhibitory cell subsets (myeloid-derived suppressor cells and regulatory T cells). We observed a minor decrease and modulation of NK cells, but for all other populations no effects could be detected. Together, these data support a strategy for combining 5-Azacytidine treatment with immune therapy for potential clinical benefit.

摘要翻译： 

使用去甲基化药物5-氮杂胞苷治疗可延长骨髓增生异常综合征患者的生存期，且该去甲基化过程可诱导癌睾抗原的上调。癌睾抗原是癌症免疫识别中众所周知的靶点，免疫系统可能在该治疗方案中发挥作用。本文研究表明，5-氮杂胞苷治疗能增强T细胞对肿瘤细胞的识别。治疗前即可检测到针对多种癌睾抗原的T细胞应答，且在治疗启动后这些应答被进一步诱导。这些特性表明5-氮杂胞苷与免疫疗法可实现理想组合，从而优先增强针对癌睾抗原的T细胞应答。为启动此类联合治疗，需要掌握关于5-氮杂胞苷总体免疫调节作用的基础知识。因此我们检测了该治疗对免疫刺激细胞（CD8+T细胞、CD4+T细胞和自然杀伤细胞）及免疫抑制细胞亚群（髓源性抑制细胞和调节性T细胞）的潜在影响。观察到自然杀伤细胞出现轻微减少和功能调整，而其他所有细胞群均未检测到变化。这些数据共同支持将5-氮杂胞苷治疗与免疫疗法联合应用于临床获益的策略。

原文链接：

5-Azacytidine treatment sensitizes tumor cells to T-cell mediated cytotoxicity and modulates NK cells in patients with myeloid malignancies