αPD-L1-armed γδ T Cells Show Enhanced Anti-tumor Activity and Reprogram the Tumor Microenvironment via Chemokine Signaling to Potentiate CD8⁺ T-Cell Recruitment and Anti-Tumor Immunity (IMAGE)
Caption
Using the fast metabolic glycan labeling (fMGL) technique, AMS-ManNAz-P was incorporated into the terminal sialic acids of various cell-surface glycans on γδ T cells. The modified γδ T cells were then conjugated with αPD-L1 via copper-free click chemistry to produce the αPD-L1–γδ T cell conjugates. The targeting antibody αPD-L1 on the conjugates first facilitates γδ T cell binding to PD-L1–expressing cancer cells, which subsequently triggers interactions between TCR γδ and BTN3A1/2A1, co-stimulatory receptors and ligands, as well as death ligands and receptors. This activation leads γδ T cells to release cytotoxic cytokines. In cancer cells, caspase-3 is activated and cleaves GSDME, initiating pyroptosis. Within the tumor microenvironment (TME), CCL5 was released from the culture of αPD-L1–γδ T cells and tumor cells, thereby recruiting and activating CD8⁺ T cells via the CCR5/CCL5 axis, ultimately remodeling the TME.
Credit
©Science China Press
Usage Restrictions
Use with credit.
License
Original content