Associations among the mutational landscape, immune microenvironment, and prognosis in Chinese patients with hepatocellular carcinoma
Associations among the mutational landscape, immune microenvironment, and prognosis in Chinese patients with hepatocellular carcinoma
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中国肝细胞癌患者的突变景观、免疫微环境和预后之间的关联
DOI：
10.1007/s00262-020-02685-7
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发表时间：
2020-08-06
影响因子：
5.8
通讯作者：
Zhou, Shao-Lai
中科院分区：
文献类型：
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作者：
Hu, Zhi-Qiang;Xin, Hao-Yang;Zhou, Shao-Lai
最近的研究表明，免疫微环境和突变景观与几种类型的癌症对基于免疫的治疗的反应有关。这些因素在中国HCC中的作用在很大程度上仍然未知。在这项研究中，我们获得了182份先前接受NGS（49份WGS，18份WES和115份靶向测序）的HCC队列FFPE样本。免疫组化检测CD 3、CD 4、CD 8、CD 57、Foxp 3、CD 68、CD 66 b、PD-L1表达。我们确定了HCC样本中突变景观和免疫微环境之间的多种关联。高突变负荷和马兜铃酸主导的突变特征均与肿瘤PD-L1表达升高和CD 3 + T细胞浸润以及大量CD 68 + TAM和CD 66 b + TAN相关。在AXIN 1/CTNNB 1突变的肿瘤和黄曲霉毒素显性突变的肿瘤中，CD 4+和CD 8 + T细胞的浸润水平较低。此外，与没有TP 53突变的肿瘤相比，具有TP 53突变的肿瘤具有较少的CD 8 + T细胞浸润和较多的Foxp 3 + Treg细胞浸润。Kaplan-Meier生存分析显示，CD 8+、Foxp 3+、CD 66 b+或CD 68+免疫细胞的存在;肿瘤PD-L1单独表达;或CD 8+或Foxp 3+细胞联合TP 53突变的存在预测根治性切除术后复发和总生存率低。总之，突变景观和免疫微环境之间的关联需要进一步分析，以确定其对患者结局的影响，以指导中国HCC患者的个性化免疫治疗。
Recent studies suggested that the immune microenvironment and mutational landscape are associated with the response to immune-based therapy in several types of cancer. The roles of those factors in Chinese HCC remain largely unknown. In this study, we obtained 182 FFPE samples of HCC cohort that were previously subjected to NGS (49 WGS, 18 WES, and 115 targeted sequencing). We performed immunohistochemistry to detect CD3, CD4, CD8, CD57, Foxp3, CD68, CD66b, and PD-L1 expression in the samples. We identified diverse associations between the mutational landscape and the immune microenvironment in the HCC samples. High mutational burden and an aristolochic acid-dominated mutational signature were both correlated with elevated tumoral PD-L1 expression and CD3+ T-cell infiltration and high numbers of CD68+ TAMs and CD66b+ TANs. CD4+ and CD8+ T cells exhibited lower infiltration levels in tumors with mutations inAXIN1/CTNNB1and in tumors with aflatoxin-dominant mutational signatures. Moreover, tumors withTP53mutations had less CD8+ T-cell infiltration and more Foxp3+ Treg-cell infiltration than those withoutTP53mutations. Kaplan–Meier survival analysis revealed that the presence of CD8+, Foxp3+, CD66b+, or CD68+ immune cells; tumoral PD-L1 expression alone; or the presence of CD8+ or Foxp3+ cells combined withTP53mutation were predictive of recurrence and poor overall survival after curative resection. In conclusion, the association between the mutational landscape and the immune microenvironment warrants further analysis to determine its impact on patient outcomes to guide personalized immune-based therapy for Chinese patients with HCC.