Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, PR China.
Department of Respirology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, PR China.
PLoS One. 2020 Apr 2;15(4):e0231003. doi: 10.1371/journal.pone.0231003. eCollection 2020.
Systematic interrogation of tumor-infiltrating immune cells (TIICs) is key to the prediction of clinical outcome and development of immunotherapies. However, little is known about the TIICs of hepatocellular carcinoma (HCC) and its impact on the prognosis of patients and potential for immunotherapy. We applied CIBERSORT of 1090 tumors to infer the infiltration of 22 subsets of TIICs using gene expression data. Unsupervised clustering analysis by 22 TIICs revealed 4 clusters of tumors, mainly defined by macrophages and T cells, with distinct prognosis and associations with immune checkpoint molecules, including PD-1, CD274, CTLA-4, LAG-3 and IFNG. We found tumors with decreased number of M1 macrophages or increased regulatory T cells were associated with poor prognosis. Based on the multivariate Cox analysis, a nomogram was also established for clinical application. In conclusion, composition of the TIICs in HCC was quite different, which is an important determinant of prognosis with great potential to identify candidates for immunotherapy.
系统分析肿瘤浸润免疫细胞(TIICs)是预测临床结局和开发免疫疗法的关键。然而,对于肝癌(HCC)的 TIIC 及其对患者预后和免疫治疗潜力的影响知之甚少。我们应用 1090 个肿瘤的 CIBERSORT,使用基因表达数据推断 22 种 TIIC 亚群的浸润情况。通过 22 种 TIIC 的无监督聚类分析,揭示了主要由巨噬细胞和 T 细胞定义的 4 个肿瘤簇,具有不同的预后,并与免疫检查点分子(包括 PD-1、CD274、CTLA-4、LAG-3 和 IFNG)相关。我们发现,M1 巨噬细胞数量减少或调节性 T 细胞增加的肿瘤与预后不良相关。基于多变量 Cox 分析,还为临床应用建立了一个列线图。总之,HCC 的 TIIC 组成差异很大,这是预后的一个重要决定因素,具有很大的潜力来确定免疫治疗的候选者。