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肝癌长期生存者中独特的 TP53 新抗原和免疫微环境。

Unique TP53 neoantigen and the immune microenvironment in long-term survivors of Hepatocellular carcinoma.

机构信息

Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC and Chinese Academy of Medical Sciences, Beijing, 100730, China.

Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China.

出版信息

Cancer Immunol Immunother. 2021 Mar;70(3):667-677. doi: 10.1007/s00262-020-02711-8. Epub 2020 Sep 2.

Abstract

Neoantigens are T-cell antigens derived from protein-coding mutations in tumor cells. Although neoantigens have recently been linked to anti-tumor immunity in long-term survivors of cancers such as melanoma, their prognostic and immune-modulatory role in many cancer types remain unexplored. We investigate neoantigens in hepatocellular carcinoma (HCC) through a combination of whole exome sequencing (WES), RNA sequencing (RNA-seq), computational bioinformation, and immunohistochemistry. Our analysis reveals that patients carried with TP53 neoantigen have a longer overall survival than others (p = 0.0371) and they showed higher Immune score (p = 0.0441), higher cytotoxic lymphocytes infiltration (p = 0.0428), and higher CYT score (p = 0.0388). In contrast, the prognosis is not associated with TMB and neoantigen load. Our study draws a preliminary conclusion that it is not TMB or neoantigen load but the TP53 specific neoantigen is related to overall survival of HCC patients. We suggest that the TP53 neoantigen may affect prognosis by regulating anti-tumor immunity and that the TP53 neoantigen may be harnessed as potential targets for immunotherapies of HCC.

摘要

新抗原是源自肿瘤细胞中蛋白编码突变的 T 细胞抗原。尽管新抗原最近与黑色素瘤等癌症的长期幸存者的抗肿瘤免疫有关,但它们在许多癌症类型中的预后和免疫调节作用仍未得到探索。我们通过全外显子组测序 (WES)、RNA 测序 (RNA-seq)、计算生物信息学和免疫组织化学相结合的方法研究肝细胞癌 (HCC) 中的新抗原。我们的分析表明,携带 TP53 新抗原的患者的总生存期比其他患者更长 (p=0.0371),并且他们的免疫评分更高 (p=0.0441)、细胞毒性淋巴细胞浸润更高 (p=0.0428) 和 CYT 评分更高 (p=0.0388)。相比之下,预后与 TMB 和新抗原负荷无关。我们的研究得出初步结论,与 HCC 患者的总生存期相关的不是 TMB 或新抗原负荷,而是 TP53 特异性新抗原。我们认为,TP53 新抗原可能通过调节抗肿瘤免疫来影响预后,并且 TP53 新抗原可能被用作 HCC 免疫治疗的潜在靶点。

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