Endosialin-positive CAFs promote hepatocellular carcinoma progression by suppressing CD8+ T cell infiltration
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View abstract on PubMed
Summary
This summary is machine-generated.Endosialin in hepatocellular carcinoma (HCC) suppresses CD8+ T cell infiltration by reducing CXCL9/10. Targeting endosialin with antibodies enhances anti-PD-1 therapy, offering a new strategy for HCC treatment.
Area Of Science
- Immunology
- Oncology
- Molecular Biology
Background
- Endosialin (CD248) is expressed in cancer-associated fibroblasts (CAFs) in hepatocellular carcinoma (HCC).
- Previous studies linked endosialin-positive CAFs to macrophage recruitment and M2 polarization in HCC.
- The role of endosialin in regulating other immune cells and promoting HCC progression remained unclear.
Purpose Of The Study
- To investigate the role of endosialin in regulating immune cell infiltration in hepatocellular carcinoma.
- To elucidate the mechanism by which endosialin influences CD8+ T cell infiltration.
- To evaluate the therapeutic potential of targeting endosialin in combination with PD-1 blockade for HCC treatment.
Main Methods
- Utilized endosialin knockout (EN<sup>KO</sup>) mice for subcutaneous and orthotopic HCC tumor models.
- Employed single-cell sequencing and flow cytometry to analyze immune cell infiltration.
- Conducted in vitro co-culture assays, chemokine arrays, RNA sequencing, and antibody blocking experiments.
Main Results
- Endosialin knockout significantly inhibited HCC tumor growth and increased CD8+ T cell infiltration.
- Endosialin was found to inhibit STAT1 phosphorylation and nuclear translocation in CAFs, reducing CXCL9/10 secretion.
- Reduced CXCL9/10 expression led to suppressed CD8+ T cell infiltration, correlating with high endosialin levels in HCC patients.
- Combination therapy with endosialin and PD-1 antibodies demonstrated synergistic antitumor effects.
Conclusions
- Endosialin promotes HCC progression by inhibiting CD8+ T cell infiltration via the CXCL9/10 pathway in CAFs.
- Targeting endosialin with antibodies can enhance the antitumor efficacy of PD-1 blockade in HCC.
- This combination therapy holds promise for overcoming resistance to PD-1-based immunotherapy in HCC.
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