Association between APOBEC3H-Mediated Demethylation and Immune Landscape in Head and Neck Squamous Carcinoma
Association between APOBEC3H-Mediated Demethylation and Immune Landscape in Head and Neck Squamous Carcinoma
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APOBEC3H 介导的去甲基化与头颈鳞状细胞癌免疫景观之间的关联
DOI：
10.1155/2020/4612375
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发表时间：
2020-07-25
影响因子：
--
通讯作者：
Ren, Xian-yue
中科院分区：
文献类型：
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作者：
Liu, Qin;Luo, Yue-wen;Ren, Xian-yue
免疫治疗已被证明是控制头颈部鳞状细胞癌（HNSC）的一种有前途的策略。AID/APOBEC家族被充分表征为DNA突变体，并被认为在HNSC的免疫应答中起关键作用。然而，AID/APOBECs在HNSC中的表达模式和脱氨基依赖性去甲基化作用尚不清楚。在这项研究中，来自TCGA数据库和基于细胞的实验的HNSC的RNA-seq和DNA甲基化谱被应用于分析AID/APOBEC表达水平、患者的临床结果、甲基化改变和免疫应答之间的关系。在这里，我们发现APOBEC 3 H在HNSC患者中异常上调。HPV+患者倾向于具有比HPV-患者更高的APOBEC 3 H水平。值得注意的是，具有高APOBEC 3 H水平的患者显示出有利的总生存期。此外，具有高APOBEC 3 H水平的肿瘤表现出全基因组DNA低甲基化模式。APOBEC 3 H被鉴定为去甲基化和上调CXCL 10并改善肿瘤微环境中的CD 8 + T细胞肿瘤浸润。总之，APOBEC 3 H在HNSC中的CD 8 + T细胞免疫浸润和活化中起关键作用，其可能是HNSC中肿瘤免疫治疗的潜在生物标志物。
Immunotherapy has been demonstrated as a promising strategy in controlling head and neck squamous cell carcinoma (HNSC). The AID/APOBEC family is well characterized as DNA mutator and considered to play critical roles in immune responses in HNSC. However, the expression pattern and deamination-dependent demethylation roles of AID/APOBECs in HNSC are unclear. In this study, the RNA-seq and DNA methylation profiles of HNSC from TCGA database and cell-based experiments were applied to analyze the relationships between AID/APOBEC expression levels, patients' clinical outcomes, methylation alterations, and immune responses. Here, we found that APOBEC3H was abnormally upregulated in HNSC patients. HPV+ patients tended to have higher APOBEC3H levels than HPV- patients. Remarkably, patients with high APOBEC3H levels showed a favorable overall survival. Furthermore, tumors with high APOBEC3H levels exhibited a genome-wide DNA hypomethylation pattern. APOBEC3H was identified to demethylate and upregulate CXCL10 and improve CD8+ T cell tumor infiltration in the tumor microenvironment. Collectively, APOBEC3H plays critical roles in CD8+ T cell immune infiltration and activation in HNSC, which may be a potential biomarker for oncoimmunotherapy in HNSC.