T cell-intrinsic VISTA expression promotes resistance to CTLA-4 blockade by restricting CD8+ T cell responses - PubMed
4 hours ago
- #CD8+ T cells
- #VISTA
- #CTLA-4
- VISTA is an immune checkpoint protein that impairs antitumor T cell responses.
- T cell-intrinsic VISTA deletion enhances early priming and short-term expansion of CD8+ T cells but fails to ensure durable tumor control.
- Persistent dysfunction in VISTA-deficient T cells is partly driven by trans-VISTA on myeloid cells and CTLA-4 upregulation.
- Combining T cell-intrinsic VISTA deficiency with CTLA-4 blockade improves T cell survival and broadens TCR repertoire diversity, leading to stronger tumor regression.
- A transcriptional signature in VISTA-deficient cytotoxic T cells correlates with better outcomes in cancer patients treated with immune checkpoint inhibitors.
- T cell-intrinsic VISTA mechanisms enforce T cell dysfunction, highlighting its potential as a therapeutic target and biomarker for immunotherapy resistance.