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  • Elucidating the role of S100A10 in CD8+ T cell exhaustion and HCC immune escape via the cPLA2 and 5-LOX axis.

Elucidating the role of S100A10 in CD8+ T cell exhaustion and HCC immune escape via the cPLA2 and 5-LOX axis.

Cell death & disease (2024-08-09)
Ganggang Wang, Xiaowei Shen, Wenzhi Jin, Chao Song, Meiyuan Dong, Zhijie Zhou, Xiaoliang Wang
ABSTRACT

Hepatocellular carcinoma (HCC) is a common malignant tumor with a complex immune evasion mechanism posing a challenge to treatment. The role of the S100A10 gene in various cancers has garnered significant attention. This study aims to elucidate the impact of S100A10 on CD8+ T cell exhaustion via the cPLA2 and 5-LOX axis, thereby elucidating its role in immune evasion in HCC. By analyzing the HCC-related data from the GEO and TCGA databases, we identified differentially expressed genes associated with lipid metabolism and developed a prognostic risk model. Subsequently, through RNA-seq and PPI analyses, we determined vital lipid metabolism genes and downstream factors S100A10, ACOT7, and SMS, which were significantly correlated with CD8+ T cell infiltration. Given the most significant expression differences, we selected S100A10 for further investigation. Both in vitro and in vivo experiments were conducted, including co-culture experiments of CD8+ T cells with MHCC97-L cells, Co-IP experiments, and validation in an HCC mouse model. S100A10 was significantly overexpressed in HCC tissues and potentially regulates CD8+ T cell exhaustion and lipid metabolism reprogramming through the cPLA2 and 5-LOX axis. Silencing S100A10 could inhibit CD8+ T cell exhaustion, further suppressing immune evasion in HCC. S100A10 may activate the cPLA2 and 5-LOX axis, initiating lipid metabolism reprogramming and upregulating LTB4 levels, thus promoting CD8+ T cell exhaustion in HCC tissues, facilitating immune evasion by HCC cells, ultimately impacting the growth and migration of HCC cells. This research highlights the critical role of S100A10 via the cPLA2 and 5-LOX axis in immune evasion in HCC, providing new theoretical foundations and potential targets for diagnosing and treating HCC.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-S100A10 antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Anti-ALOX5 antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Anti-Phospholipase A2 (CPLA2) antibody produced in rabbit, ~1.5 mg/mL, affinity isolated antibody