Single-cell RNA Sequencing Shows the Immunosuppressive Landscape and Tumor Heterogeneity of HBV-associated Hepatocellular Carcinoma

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Jun 18

PMID 34140495

Citations 131

Authors

Daniel Wai-Hung Ho

Yu-Man Tsui

Lo-Kong Chan

Karen Man-Fong Sze

Xin Zhang

Jacinth Wing-Sum Cheu

Yung-Tuen Chiu

Joyce Man-Fong Lee

Albert Chi-Yan Chan

Elaine Tin-Yan Cheung

Derek Tsz-Wai Yau

Nam-Hung Chia

Irene Lai-Oi Lo

Pak-Chung Sham

Tan-To Cheung

Carmen Chak-Lui Wong

Irene Oi-Lin Ng

Affiliations

Soon will be listed here.

Abstract

Interaction between tumor cells and immune cells in the tumor microenvironment is important in cancer development. Immune cells interact with the tumor cells to shape this process. Here, we use single-cell RNA sequencing analysis to delineate the immune landscape and tumor heterogeneity in a cohort of patients with HBV-associated human hepatocellular carcinoma (HCC). We found that tumor-associated macrophages suppress tumor T cell infiltration and TIGIT-NECTIN2 interaction regulates the immunosuppressive environment. The cell state transition of immune cells towards a more immunosuppressive and exhaustive status exemplifies the overall cancer-promoting immunocellular landscape. Furthermore, the heterogeneity of global molecular profiles reveals co-existence of intra-tumoral and inter-tumoral heterogeneity, but is more apparent in the latter. This analysis of the immunosuppressive landscape and intercellular interactions provides mechanistic information for the design of efficacious immune-oncology treatments in hepatocellular carcinoma.

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