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

Yang, Huayu; Sun, Lejia; Guan, Ai; Yin, Huanhuan; Liu, Meixi; Mao, Xinxin; Xu, Haifeng; Zhao, Haitao; Lu, Xin; Sang, Xinting; Zhong, Shouxian; Chen, Qian; Mao, Yilei

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.

Cancer Immunology, Immunotherapy, 2021, Vol 70, Issue 3, p667

0340-7004

Academic Journal

10.1007/s00262-020-02711-8