dataset
posted on 2023-03-31, 21:51 authored by Manling Huang, Minghui He, Yu Guo, Heping Li, Shunli Shen, Yubin Xie, Xiaoxing Li, Han Xiao, Lujing Fang, Dongming Li, Baogang Peng, Lijian Liang, Jun Yu, Ming Kuang, Lixia Xu, Sui Peng Table S5 shows detailed information of structure variations in the six HCC patients with WGS analysis.
Funding
National Natural Science Foundation of China
Bureau of Science and Information Technology of Guangzhou Municipality
Pearl River S and T Nova Program of Guangzhou
Guangdong Natural Science Foundation
Guangzhou Research Collaborative Innovation Projects
History
ARTICLE ABSTRACT
Immune checkpoint inhibitor therapy is emerging as the promising option for patients with advanced hepatocellular carcinoma. We aimed to investigate the heterogeneity of different tumor nodules of the same patient with multifocal hepatocellular carcinomas in response to immunotherapy and its molecular mechanisms.
We attained 45 surgical tumor samples including 33 small and 12 large nodules from 12 patients with multifocal hepatocellular carcinoma and evaluated genomic and immune heterogeneity among tumors through whole-genome sequencing and RNA sequencing. IHC was performed to validate the expression of immune markers. The responses to anti–programmed cell death protein-1 (PD-1) therapy in patients with multifocal hepatocellular carcinoma were evaluated.
The small and large tumors within the same patient presented with similar genomic characteristics, indicating their same genomic origin. We further found the small tumors had higher immune cell infiltration including more CD8+ T cells, M1 macrophages, and monocytes as compared with large tumors. Besides, the expression of interferon signature predictive of response to anti–PD-1 therapy was significantly upregulated in the small tumors. Moreover, the immune pathways were more vigorous along with less active proliferation pathways in the small tumors. In keeping with this, we found that small nodules were more sensitive to anti–PD-1 therapy than large nodules in patients with multifocal hepatocellular carcinoma.
The small tumors in patients with multifocal hepatocellular carcinoma had higher immune cell infiltration and upregulation of immune pathways as compared with the large tumors, which can partially explain the different responses of small and large tumors in the same case to anti–PD-1 therapy.
