Dual regulation of CXCR6+CD8+ T cells modulates cytotoxic and exhaustion-associated programs during prostate cancer progression - PubMed
a day ago
- #T cell
- #Prostate Cancer
- #Immunotherapy
- Prostate cancer (PCa) is immunologically 'cold' with limited effector T cells and poor response to immune checkpoint blockade.
- CXCR6+CD8+ T cells are highly cytotoxic but their role in PCa is not well understood.
- Single-cell RNA sequencing and immunofluorescence were used to analyze CXCR6+CD8+ T cells in PCa.
- CXCR6+CD8+ T cells decline with increasing Gleason Score (GS) in PCa.
- M1-like macrophages secrete CXCL16, which maintains CXCR6+CD8+ T cells in tumors.
- Loss of M1-like macrophages in advanced tumors leads to depletion of CXCR6+CD8+ T cells.
- CXCR6+CD8+ T cells are essential for antitumor immunity; their depletion accelerates tumor growth.
- FOXO1-KLF2 axis transcriptionally represses CXCR6 expression.
- IL-10-STAT3 signaling upregulates FOXO1 and KLF2, suppressing CXCR6 and impairing cytotoxicity.
- Pharmacologic inhibition of FOXO1 enhances CXCR6+CD8+ T cell expansion and synergizes with anti-PD-1 therapy.
- Targeting FOXO1 or IL-10 could restore CXCR6+CD8+ T cell immunity and improve PCa immunotherapy.