作者
Yun‐Fan Sun,Liang Wu,Yu Zhang,Kaiyu Zhou,Yong Hou,Zifei Wang,Zefan Zhang,Junping Xie,Chunqing Wang,Dandan Chen,Yaling Huang,Xiaochan Wei,Ying–Hong Shi,Zhikun Zhao,Yuehua Li,Ziwei Guo,Qichao Yu,Liqin Xu,Giacomo Volpe,Shuang‐Jian Qiu,Jian Zhou,Carl Ward,Hui‐Chuan Sun,Ye Yin,Xun Xu,Xiangdong Wang,Miguel A. Esteban,Huanming Yang,Jian Wang,Michael Dean,Yaguang Zhang,Shiping Liu,Xin‐Rong Yang,Jia Fan
摘要
Hepatocellular carcinoma (HCC) has high relapse and low 5-year survival rates. Single-cell profiling in relapsed HCC may aid in the design of effective anticancer therapies, including immunotherapies. We profiled the transcriptomes of ∼17,000 cells from 18 primary or early-relapse HCC cases. Early-relapse tumors have reduced levels of regulatory T cells, increased dendritic cells (DCs), and increased infiltrated CD8+ T cells, compared with primary tumors, in two independent cohorts. Remarkably, CD8+ T cells in recurrent tumors overexpressed KLRB1 (CD161) and displayed an innate-like low cytotoxic state, with low clonal expansion, unlike the classical exhausted state observed in primary HCC. The enrichment of these cells was associated with a worse prognosis. Differential gene expression and interaction analyses revealed potential immune evasion mechanisms in recurrent tumor cells that dampen DC antigen presentation and recruit innate-like CD8+ T cells. Our comprehensive picture of the HCC ecosystem provides deeper insights into immune evasion mechanisms associated with tumor relapse.