Multiregional single-cell dissection of tumor and immune cells reveals stable lock-and-key features in liver cancer.

Abstract

Intratumor heterogeneity may result from the evolution of tumor cells and their continuous interactions with the tumor microenvironment which collectively drives tumorigenesis. However, an appearance of cellular and molecular heterogeneity creates a challenge to define molecular features linked to tumor malignancy. Here we perform multiregional single-cell RNA sequencing (scRNA-seq) analysis of seven liver cancer patients (four hepatocellular carcinoma, HCC and three intrahepatic cholangiocarcinoma, iCCA). We identify cellular dynamics of malignant cells and their communication networks with tumor-associated immune cells, which are validated using additional scRNA-seq data of 25 HCC and 12 iCCA patients as a stable fingerprint embedded in a malignant ecosystem representing features of tumor aggressiveness. We further validate the top ligand-receptor interaction pairs (i.e., LGALS9-SLC1A5 and SPP1-PTGER4 between tumor cells and macrophages) associated with unique transcriptome in additional 542 HCC patients. Our study unveils stable molecular networks of malignant ecosystems, which may open a path for therapeutic exploration.

• Authors: Lichun Ma, Sophia Heinrich, Limin Wang, Friederike L Keggenhoff, Subreen Khatib, Marshonna Forgues, Michael Kelly, Stephen M Hewitt, Areeba Saif, Jonathan M Hernandez, Donna Mabry, Roman Kloeckner, Tim F Greten, Jittiporn Chaisaingmongkol, Mathuros Ruchirawat, Jens U Marquardt, Xin Wei Wang
• Journal: Nature communications (Nat Commun) Vol. 13 Issue 1 Pg. 7533 (12 07 2022) ISSN: 2041-1723 [Electronic] England
• PMID: 36476645 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

Chemical References

• SLC1A5 protein, human
• Minor Histocompatibility Antigens
• Amino Acid Transport System ASC

Topics

• Humans
• Liver Neoplasms (genetics)
• Carcinoma, Hepatocellular (genetics)
• Ecosystem
• Tumor Microenvironment (genetics)
• Minor Histocompatibility Antigens
• Amino Acid Transport System ASC