Cargando…
Ultrarapid lytic granule release from CTLs activates Ca(2+)-dependent synaptic resistance pathways in melanoma cells
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 mela...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8849291/ https://www.ncbi.nlm.nih.gov/pubmed/35171665 http://dx.doi.org/10.1126/sciadv.abk3234 |
_version_ | 1784652432221929472 |
---|---|
author | Filali, Liza Puissegur, Marie-Pierre Cortacero, Kevin Cussat-Blanc, Sylvain Khazen, Roxana Van Acker, Nathalie Frenois, François-Xavier Abreu, Arnaud Lamant, Laurence Meyer, Nicolas Vergier, Béatrice Müller, Sabina McKenzie, Brienne Valitutti, Salvatore |
author_facet | Filali, Liza Puissegur, Marie-Pierre Cortacero, Kevin Cussat-Blanc, Sylvain Khazen, Roxana Van Acker, Nathalie Frenois, François-Xavier Abreu, Arnaud Lamant, Laurence Meyer, Nicolas Vergier, Béatrice Müller, Sabina McKenzie, Brienne Valitutti, Salvatore |
author_sort | Filali, Liza |
collection | PubMed |
description | 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 Ca(2+) 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 Ca(2+) flux and silencing of synaptotagmin VII limited synaptic lysosomal exposure and enhanced cytotoxicity. Multiplexed immunohistochemistry of patient melanoma nodules combined with automated image analysis showed that melanoma cells facing CD8(+) CTLs in the tumor periphery or peritumoral area exhibited significant lysosomal enrichment. Our results identified synaptic Ca(2+) entry as the definitive trigger for lysosomal deployment to the synapse upon CTL attack and highlighted an unpredicted defensive topology of lysosome distribution in melanoma nodules. |
format | Online Article Text |
id | pubmed-8849291 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-88492912022-03-04 Ultrarapid lytic granule release from CTLs activates Ca(2+)-dependent synaptic resistance pathways in melanoma cells Filali, Liza Puissegur, Marie-Pierre Cortacero, Kevin Cussat-Blanc, Sylvain Khazen, Roxana Van Acker, Nathalie Frenois, François-Xavier Abreu, Arnaud Lamant, Laurence Meyer, Nicolas Vergier, Béatrice Müller, Sabina McKenzie, Brienne Valitutti, Salvatore Sci Adv Biomedicine and Life Sciences 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 Ca(2+) 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 Ca(2+) flux and silencing of synaptotagmin VII limited synaptic lysosomal exposure and enhanced cytotoxicity. Multiplexed immunohistochemistry of patient melanoma nodules combined with automated image analysis showed that melanoma cells facing CD8(+) CTLs in the tumor periphery or peritumoral area exhibited significant lysosomal enrichment. Our results identified synaptic Ca(2+) entry as the definitive trigger for lysosomal deployment to the synapse upon CTL attack and highlighted an unpredicted defensive topology of lysosome distribution in melanoma nodules. American Association for the Advancement of Science 2022-02-16 /pmc/articles/PMC8849291/ /pubmed/35171665 http://dx.doi.org/10.1126/sciadv.abk3234 Text en Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Filali, Liza Puissegur, Marie-Pierre Cortacero, Kevin Cussat-Blanc, Sylvain Khazen, Roxana Van Acker, Nathalie Frenois, François-Xavier Abreu, Arnaud Lamant, Laurence Meyer, Nicolas Vergier, Béatrice Müller, Sabina McKenzie, Brienne Valitutti, Salvatore Ultrarapid lytic granule release from CTLs activates Ca(2+)-dependent synaptic resistance pathways in melanoma cells |
title | Ultrarapid lytic granule release from CTLs activates Ca(2+)-dependent synaptic resistance pathways in melanoma cells |
title_full | Ultrarapid lytic granule release from CTLs activates Ca(2+)-dependent synaptic resistance pathways in melanoma cells |
title_fullStr | Ultrarapid lytic granule release from CTLs activates Ca(2+)-dependent synaptic resistance pathways in melanoma cells |
title_full_unstemmed | Ultrarapid lytic granule release from CTLs activates Ca(2+)-dependent synaptic resistance pathways in melanoma cells |
title_short | Ultrarapid lytic granule release from CTLs activates Ca(2+)-dependent synaptic resistance pathways in melanoma cells |
title_sort | ultrarapid lytic granule release from ctls activates ca(2+)-dependent synaptic resistance pathways in melanoma cells |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8849291/ https://www.ncbi.nlm.nih.gov/pubmed/35171665 http://dx.doi.org/10.1126/sciadv.abk3234 |
work_keys_str_mv | AT filaliliza ultrarapidlyticgranulereleasefromctlsactivatesca2dependentsynapticresistancepathwaysinmelanomacells AT puissegurmariepierre ultrarapidlyticgranulereleasefromctlsactivatesca2dependentsynapticresistancepathwaysinmelanomacells AT cortacerokevin ultrarapidlyticgranulereleasefromctlsactivatesca2dependentsynapticresistancepathwaysinmelanomacells AT cussatblancsylvain ultrarapidlyticgranulereleasefromctlsactivatesca2dependentsynapticresistancepathwaysinmelanomacells AT khazenroxana ultrarapidlyticgranulereleasefromctlsactivatesca2dependentsynapticresistancepathwaysinmelanomacells AT vanackernathalie ultrarapidlyticgranulereleasefromctlsactivatesca2dependentsynapticresistancepathwaysinmelanomacells AT frenoisfrancoisxavier ultrarapidlyticgranulereleasefromctlsactivatesca2dependentsynapticresistancepathwaysinmelanomacells AT abreuarnaud ultrarapidlyticgranulereleasefromctlsactivatesca2dependentsynapticresistancepathwaysinmelanomacells AT lamantlaurence ultrarapidlyticgranulereleasefromctlsactivatesca2dependentsynapticresistancepathwaysinmelanomacells AT meyernicolas ultrarapidlyticgranulereleasefromctlsactivatesca2dependentsynapticresistancepathwaysinmelanomacells AT vergierbeatrice ultrarapidlyticgranulereleasefromctlsactivatesca2dependentsynapticresistancepathwaysinmelanomacells AT mullersabina ultrarapidlyticgranulereleasefromctlsactivatesca2dependentsynapticresistancepathwaysinmelanomacells AT mckenziebrienne ultrarapidlyticgranulereleasefromctlsactivatesca2dependentsynapticresistancepathwaysinmelanomacells AT valituttisalvatore ultrarapidlyticgranulereleasefromctlsactivatesca2dependentsynapticresistancepathwaysinmelanomacells |