PRDX2 induces tumor immune evasion by modulating the HDAC3-Galectin-9 axis in lung adenocarcinoma cells

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Peroxiredoxin 2 (PRDX2) is upregulated in many cancers, promoting tumor cell proliferation.
• Its specific role in tumor immunity, particularly in lung adenocarcinoma, is not fully understood.
• PRDX2's impact on T cells within the tumor microenvironment and its contribution to immune escape require investigation.

Purpose of the Study:

• To investigate the effect of PRDX2 on T cells in the lung adenocarcinoma immune microenvironment.
• To identify PRDX2's immune target that facilitates lung cancer cell immune escape.
• To provide a theoretical basis for targeting PRDX2 in lung adenocarcinoma treatment.

Main Methods:

• Utilized mouse models to assess Conoidin A's effect on tumor growth and T cell infiltration.
• Employed flow cytometry and Western blot to analyze tumor cell apoptosis and T cell cytotoxic markers (granzyme B, perforin).
• Applied RNA-Seq for downstream immune molecule identification and si-RNA knockdown for Galectin-9, alongside immunofluorescence and Western blot to confirm PRDX2-HDAC3-Galectin-9 regulation.

Main Results:

• PRDX2 expression inversely correlated with CD8+ T cell levels in lung adenocarcinoma patients.
• PRDX2 inhibition significantly improved T cell-mediated killing of lung adenocarcinoma cells and reduced tumor burden in vitro and in vivo.
• Mechanistically, PRDX2 inhibition reduced Galectin-9 expression via down-regulation of phosphorylated HDAC3, enhancing CD8+ T cell infiltration and function.

Conclusions:

• The PRDX2/HDAC3/Galectin-9 axis plays a critical role in lung adenocarcinoma immune escape.
• Galectin-9 emerges as a potential therapeutic target for enhancing lung adenocarcinoma immunotherapy.