Single-cell RNA sequencing shows the immunosuppressive landscape and tumor heterogeneity of HBV-associated hepatocellular carcinoma

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 and Irene Oi-Lin Ng ()
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Daniel Wai-Hung Ho: The University of Hong Kong
Yu-Man Tsui: The University of Hong Kong
Lo-Kong Chan: The University of Hong Kong
Karen Man-Fong Sze: The University of Hong Kong
Xin Zhang: The University of Hong Kong
Jacinth Wing-Sum Cheu: The University of Hong Kong
Yung-Tuen Chiu: The University of Hong Kong
Joyce Man-Fong Lee: The University of Hong Kong
Albert Chi-Yan Chan: The University of Hong Kong
Elaine Tin-Yan Cheung: Queen Elizabeth Hospital
Derek Tsz-Wai Yau: Queen Elizabeth Hospital
Nam-Hung Chia: Queen Elizabeth Hospital
Irene Lai-Oi Lo: Queen Elizabeth Hospital
Pak-Chung Sham: The University of Hong Kong
Tan-To Cheung: The University of Hong Kong
Carmen Chak-Lui Wong: The University of Hong Kong
Irene Oi-Lin Ng: The University of Hong Kong

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-24010-1

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