Accession

PRJCA041089

Title

Metabolism archetype cancer cells induce protumor TREM2+ macrophages via oxLDL-mediated metabolic interplay in hepatocellular carcinoma

Relevance

Medical

Data types

Transcriptome or Gene expression
Raw sequence reads
Single cell sequencing

Organisms

Mus musculus
Homo sapiens

Description

The functional programs adopted by cancer cells and their impact on the tumor microenvironment are complex and remain elusive. Here, we identify three distinct single-cell archetypes (i.e. metabolism, stemness and inflammation) in hepatocellular carcinoma (HCC) cells, each exhibiting unique spatial distribution. Further analysis reveals an immune-suppressive niche orchestrated by metabolism archetype cancer cells and TREM2-positive tumor-associated macrophages (TREM2+TAMs), which exacerbates immune exclusion and compromises patient outcomes. Mechanistically, we demonstrate that the upregulated squalene epoxidase (SQLE) expression in metabolism archetype cancer cells facilitates the generation of oxidized LDL (oxLDL). OxLDL induces TREM2+TAM polarization through the TREM2-SYK-CEBPα axis, enabling these TAMs to promote cancer cell invasion, resistance to effector cytokines and CD8+T cell dysfunction. Importantly, cancer cell-intrinsic SQLE and TREM2+TAMs are associated with inferior immunotherapy response in human and mouse HCC. Our results highlight an oxLDL-mediated metabolic interplay between cancer cells and TREM2+TAMs, offering a promising therapeutic avenue for HCC immunotherapies.

Sample scope

Multispecies

Release date

2025-06-03

Grants

Agency	program	Grant ID	Grant title
National Natural Science Foundation of China (NSFC)		NA

Submitter

Weiren Liu (liu.weiren@zs-hospital.sh.cn)

Organization

Zhongshan Hospital, Fudan University

Submission date

2025-06-03

Project Data

Resource name	Description
BioSample (33) show	-
SAMC5219735	scRNA-seq of mus musculus: adult male HCC
SAMC5219734	scRNA-seq of mus musculus: adult male HCC
SAMC5219733	scRNA-seq of mus musculus: adult male HCC
SAMC5219732	scRNA-seq of mus musculus: adult male HCC
SAMC5219731	scRNA-seq of mus musculus: adult male HCC
SAMC5219730	scRNA-seq of mus musculus: adult male HCC
SAMC5219729	scRNA-seq of mus musculus: adult male HCC
SAMC5208819	RNA-seq of mus musculus: HCC cell lines
SAMC5208818	RNA-seq of mus musculus: HCC cell lines
SAMC5208817	RNA-seq of mus musculus: HCC cell lines
SAMC5208816	RNA-seq of mus musculus: HCC cell lines
SAMC5208815	RNA-seq of mus musculus: HCC cell lines
SAMC5208814	RNA-seq of mus musculus: HCC cell lines
SAMC5208813	RNA-seq of mus musculus: isolated macrophages
SAMC5208812	RNA-seq of mus musculus: isolated macrophages
SAMC5208811	RNA-seq of mus musculus: isolated macrophages
SAMC5208810	RNA-seq of mus musculus: isolated macrophages
SAMC5208797	RNA-seq of mus musculus: HCC cell lines
SAMC5208796	RNA-seq of mus musculus: HCC cell lines
SAMC5208795	RNA-seq of mus musculus: HCC cell lines
SAMC5208794	RNA-seq of mus musculus: HCC cell lines
SAMC5208793	RNA-seq of mus musculus: HCC cell lines
SAMC5208792	RNA-seq of mus musculus: HCC cell lines
SAMC5208791	RNA-seq of mus musculus: HCC cell lines
SAMC5208790	RNA-seq of mus musculus: HCC cell lines
SAMC5208789	RNA-seq of mus musculus: HCC cell lines
SAMC5208788	RNA-seq of mus musculus: HCC cell lines
SAMC5208787	RNA-seq of mus musculus: HCC cell lines
SAMC5208786	RNA-seq of mus musculus: HCC cell lines
SAMC5208785	RNA-seq of homo sapiens: isolated macrophages
SAMC5208784	RNA-seq of homo sapiens: isolated macrophages
SAMC5208783	RNA-seq of homo sapiens: isolated macrophages
SAMC5208782	RNA-seq of homo sapiens: isolated macrophages
GSA (2)	-
CRA026592	Single cell RNA sequencing of mouse spontaneous HCC
CRA026515	RNA sequencing of macrophages and cancer cell lines