Unique TP53 neoantigen and the immune microenvironment in long-term survivors of Hepatocellular carcinoma
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ORIGINAL ARTICLE
Unique TP53 neoantigen and the immune microenvironment in long‑term survivors of Hepatocellular carcinoma Huayu Yang1 · Lejia Sun1 · Ai Guan2 · Huanhuan Yin2 · Meixi Liu2 · Xinxin Mao3 · Haifeng Xu1 · Haitao Zhao1 · Xin Lu1 · Xinting Sang1 · Shouxian Zhong1 · Qian Chen4 · Yilei Mao1 Received: 15 April 2020 / Accepted: 23 August 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
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 immunemodulatory 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. Keywords Hepatocellular carcinoma · TP53 neoantigen · Immune microenvironment · Immunotherapy Abbreviations CTLs Cytotoxic T cells CYT Cytolytic activity FFPE Formalin-fixed paraffin-embedded GZMA Granzyme A HCC Hepatocellular carcinoma IHC Immunohistochemistry Huayu Yang and Lejia Sun contributed equally to this article. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00262-020-02711-8) contains supplementary material, which is available to authorized users. * Yilei Mao pumch‑[email protected] 1
Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC and Chinese Academy of Medical Sciences, Beijing 100730, China
2
Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
3
Department of Pathology, Peking Union Medical College (PUMC) Hospital, PUMC and Chinese Academy of Medical Sciences, Beijing 100730, China
4
Thorgene Co., Ltd., Beijing, China
MHC Histocompatibility complex NSCLC Non-small cell lung cancer PRF 1 Perforin 1 PUMCH Peking Union Medical College Hospital TMB Tumor mutation burden WES Whole-exome sequencing
Introduction Hepatocellular carcinoma (HCC), the major pathological type of liver cancer (comprising 75–85% of cases), is still a leading cause of cancer-related death worldwide [1] and with very limited therapeutic options. Particularly in advanced stage, long-term survival is uncommon [2, 3
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