Neoantigen landscape in metastatic nasopharyngeal carcinoma.
Neoantigen landscape in metastatic nasopharyngeal carcinoma.
复制标题
转移性鼻咽癌中的新抗原景观
DOI：
10.7150/thno.53229
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发表时间：
2021
期刊：
影响因子：
12.4
通讯作者：
Chen MY
中科院分区：
文献类型：
--
作者：
Lin M;Zhang XL;You R;Yang Q;Zou X;Yu K;Liu YP;Zou RH;Hua YJ;Huang PY;Wang J;Zhao Q;Jiang XB;Tang J;Gu YK;Yu T;He GP;Xie YL;Wang ZQ;Liu T;Chen SY;Zuo ZX;Chen MY
背景资料：据报道，鼻咽癌（NPC）患者的MHC I类异常的生存率很低，这表明肿瘤新抗原的缺陷可能是NPC免疫监视逃逸的机制。研究方法：为了清楚地描绘NPC中新抗原的景观，我们对来自26名患者的成对原发肿瘤、区域淋巴结转移和远处转移样本进行了DNA和RNA测序。使用pVACseq流水线预测新抗原。采用随机森林算法建立亚型预测模型。结果如下：首次描绘NPC中新抗原的景观，我们发现NPC的新抗原负荷高于癌症基因组图谱计划中其他癌症的平均水平。虽然原发性肿瘤、区域淋巴结转移和远处转移样本中新抗原的数量和质量相似，但转移部位的新抗原消耗比原发性肿瘤更严重。在追踪新抗原的克隆性变化时，我们发现在转移期间发生新抗原减少。基于报告数据构建亚型预测模型，我们观察到亚型I缺乏T细胞并且遭受严重的新抗原耗竭，亚型II高表达免疫检查点分子并且遭受最少的新抗原耗竭，而亚型III是异质性的。结论：这些结果表明，新抗原有助于指导临床治疗，NPC的个体化治疗性疫苗需要更深入的基础和临床研究，使其在未来变得可行。
Background: Reportedly, nasopharyngeal carcinoma (NPC) patients with MHC I Class aberration are prone to poor survival outcomes, which indicates that the deficiency of tumor neoantigens might represent a mechanism of immune surveillance escape in NPC. Methods: To clearly delineate the landscape of neoantigens in NPC, we performed DNA and RNA sequencing on paired primary tumor, regional lymph node metastasis and distant metastasis samples from 26 patients. Neoantigens were predicted using pVACseq pipeline. Subtype prediction model was built using random forest algorithm. Results: Portraying the landscape of neoantigens in NPC for the first time, we found that the neoantigen load of NPC was above average compared to that of other cancers in The Cancer Genome Atlas program. While the quantity and quality of neoantigens were similar among primary tumor, regional lymph node metastasis and distant metastasis samples, neoantigen depletion was more severe in metastatic sites than in primary tumors. Upon tracking the clonality change of neoantigens, we found that neoantigen reduction occurred during metastasis. Building a subtype prediction model based on reported data, we observed that subtype I lacked T cells and suffered from severe neoantigen depletion, subtype II highly expressed immune checkpoint molecules and suffered from the least neoantigen depletion, and subtype III was heterogenous. Conclusions: These results indicate that neoantigens are conducive to the guidance of clinical treatment, and personalized therapeutic vaccines for NPC deserve deeper basic and clinical investigations to make them feasible in the future.