TOPK Suppresses the CD8+ T Cell Antitumor Immunity via Modulation of IRF5 Expression - PubMed
5 hours ago
- #Melanoma
- #TOPK
- #CD8+ T cells
- TOPK, a serine/threonine kinase, is overexpressed in human tumors and promotes malignant proliferation.
- Melanoma is highly immunogenic, but CD8+ T cell-mediated cytotoxicity is often ineffective in tumor control.
- Study aims to elucidate TOPK's role in CD8+ T cells during antitumor responses in melanoma.
- TOPK+ CD8+ T cells in melanoma show suppressed cytotoxic and cytokine programs.
- Genetic deletion of TOPK in CD8+ T cells enhances granzyme B, TNF-α, and IFN-γ secretion, improving tumor control.
- TOPK-deficient CD8+ T cells exhibit elevated activation-associated signaling and immune effector gene expression.
- Mechanistically, TOPK suppresses IRF5 expression; inhibition restores CD8+ T cell cytotoxicity.
- Combination of TOPK inhibitor HI-TOPK-032 and anti-PD-1 further inhibits tumor growth and boosts cytokine production.
- Enforced TOPK expression in human CD8+ T cells impairs cytotoxicity, reversible by IRF5 coexpression.
- TOPK is identified as an immune checkpoint limiting CD8+ T cell functionality in tumors.