Single-cell RNA sequencing shows the immunosuppressive landscape and tumor heterogeneity of HBV-associated hepatocellular carcinoma.
Algorithms
Animals
Carcinoma, Hepatocellular
/ genetics
Cell Proliferation
Gene Expression Regulation
/ genetics
Hepatitis B virus
/ genetics
Humans
Liver Neoplasms
/ genetics
Macrophages
/ cytology
Male
Mice
Mice, Inbred C57BL
Nectins
/ genetics
Principal Component Analysis
Prognosis
RNA-Seq
Receptors, Immunologic
/ metabolism
Single-Cell Analysis
T-Lymphocytes
/ cytology
Tumor Microenvironment
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
17 06 2021
17 06 2021
Historique:
received:
15
08
2020
accepted:
28
05
2021
entrez:
18
6
2021
pubmed:
19
6
2021
medline:
8
7
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34140495
doi: 10.1038/s41467-021-24010-1
pii: 10.1038/s41467-021-24010-1
pmc: PMC8211687
doi:
Substances chimiques
NECTIN2 protein, human
0
Nectins
0
Receptors, Immunologic
0
TIGIT protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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