Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, China; Zhong-Hua Precision Medical Center, Zhongshan Hospital, Fudan University-BGI, Shanghai 200032, China.
BGI-Shenzhen, Beishan Industrial Zone, Shenzhen 518083, China; Zhong-Hua Precision Medical Center, Zhongshan Hospital, Fudan University-BGI, Shanghai 200032, China; BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, China.
Cell. 2021 Jan 21;184(2):404-421.e16. doi: 10.1016/j.cell.2020.11.041. Epub 2020 Dec 23.
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.
肝细胞癌 (HCC) 的复发率高，5 年生存率低。对复发 HCC 的单细胞进行分析可能有助于设计有效的抗癌疗法，包括免疫疗法。我们对 18 例原发性或早期复发 HCC 病例的约 17000 个细胞的转录组进行了分析。在两个独立的队列中，与原发性肿瘤相比，早期复发肿瘤中的调节性 T 细胞水平降低，树突状细胞 (DC) 增加，浸润的 CD8 T 细胞增加。值得注意的是，与原发性 HCC 中观察到的经典耗竭状态不同，复发性肿瘤中的 CD8 T 细胞过度表达 KLRB1（CD161），并表现出先天样低细胞毒性状态，克隆扩增水平较低。这些细胞的富集与预后较差相关。差异基因表达和相互作用分析揭示了复发性肿瘤细胞中潜在的免疫逃逸机制，这些机制抑制了 DC 的抗原呈递并募集了先天样 CD8 T 细胞。我们对 HCC 生态系统的全面描述提供了对与肿瘤复发相关的免疫逃逸机制的更深入了解。
