GITR activation potentiates anti-tumor immunity of tumor-infiltrating lymphocytes expanded from glioblastoma by rescuing exhaustion - PubMed
8 hours ago
- #GITR activation
- #glioblastoma
- #TIL therapy
- Autologous tumor-infiltrating lymphocyte (TIL) therapy shows potential for solid tumors but faces limitations in glioblastoma due to T cell exhaustion and immunosuppression.
- Researchers optimized an in vitro expansion method for TILs from glioblastoma lesions and evaluated their tumor-killing capacity in vitro and in vivo.
- Single-cell RNA sequencing revealed heterogeneity in expanded TILs, identifying a cytotoxic tissue-resident memory (TRM) CD8+ TIL subset with a unique exhaustion signature.
- GITR (TNFRSF18) is highly expressed on both immunosuppressive regulatory T (Treg) cells and exhausted CD8+ TILs.
- GITR agonism via αGITR antibody enhanced CD8+ TIL activation and reduced Treg-mediated immunosuppression, synergizing with αPD-1 therapy to improve tumor control.
- GITR activation promoted immunological synapse (IS) formation and function in TILs via the NF-κB/KALRN signaling axis, boosting anti-tumor responses.
- The study positions GITR targeting as a novel strategy to enhance TIL therapy for glioblastoma, with promising clinical implications.