Tescalcin is a phagocytic checkpoint driving immune escape and limiting immunotherapeutic efficacy in hepatocellular carcinoma - PubMed
5 hours ago
- #Tescalcin
- #Immunotherapy
- #Hepatocellular Carcinoma
- Tescalcin (TESC) is identified as a phagocytic checkpoint that contributes to immune evasion and limits immunotherapeutic efficacy in hepatocellular carcinoma (HCC).
- Mechanistically, H3K4 methylation drives TESC expression in hepatoma cells, which buffers cytosolic Ca²⁺ and reduces endoplasmic reticulum stress-induced calreticulin (CALR) exposure on the plasma membrane, an essential 'eat-me' signal.
- This process impairs phagocytosis by antigen-presenting cells (APCs), such as macrophages and dendritic cells, leading to reduced antigen presentation and T-cell activation.
- Clinically, elevated H3K4me3-TESC signaling serves as a prognostic biomarker for poor response to immune checkpoint blockade (ICB) in HCC.
- Disrupting the TESC axis in vivo restores APC phagocytic function and enhances the antitumor effects of ICB therapy, suggesting a targeted therapeutic strategy for HCC immunotherapy.