Ultrarapid lytic granule release from CTLs activates Ca²⁺-dependent synaptic resistance pathways in melanoma cells.

ABSTRACT: Human cytotoxic T lymphocytes (CTLs) exhibit ultrarapid lytic granule secretion, but whether melanoma cells mobilize defense mechanisms with commensurate rapidity remains unknown. We used single-cell time-lapse microscopy to offer high spatiotemporal resolution analyses of subcellular events in melanoma cells upon CTL attack. Target cell perforation initiated an intracellular Ca²⁺ wave that propagated outward from the synapse within milliseconds and triggered lysosomal mobilization to the synapse, facilitating membrane repair and conferring resistance to CTL induced cytotoxicity. Inhibition of Ca²⁺ flux and silencing of synaptotagmin VII limited synaptic lysosomal exposure and enhanced cytotoxicity. Multiplexed immunohistochemistry of patient melanoma nodules combined

SUBMITTER: Filali L 

PROVIDER: S-EPMC8849291 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature