A ganglioside-based immune checkpoint enables senescent cells to evade immunosurveillance during aging - CNRS - Centre national de la recherche scientifique
Journal Articles Nature Aging Year : 2024

A ganglioside-based immune checkpoint enables senescent cells to evade immunosurveillance during aging

Charlène Iltis
Iryna Moskalevska
  • Function : Author
Antoine Debiesse
  • Function : Author
Centre de Recherche en Cancérologie de Lyon
Laetitia Seguin
Christina Fissoun
  • Function : Author
Ludovic Cervera
  • Function : Author
Lyvia Moudombi
  • Function : Author
Centre de Recherche en Cancérologie de Lyon
Maude Ardin
Anthony Ferrari
Synergie Lyon Cancer-Platform of Bioinformatics-Gilles Thomas
Coline Eliott
  • Function : Author
Didier Pisani
Laboratoire de PhysioMédecine Moléculaire
Alexandre Ottaviani
Manon Bourinet
  • Function : Author
Carmelo Luci
Philippe Gual
Gabriela Makulyte
David Bernard
Centre de Recherche en Cancérologie de Lyon
Manon Durandy
Lou Duret
  • Function : Author
Tynhinane Hamidouche
  • Function : Author
Sarah Kunz
  • Function : Author
Olivier Croce
Clément Delannoy
Yann Gueŕardel
Fabrice Allain
Paul Hofman
Delphine Benarroch-Popivker
  • Function : Author
Laurence Bianchini
  • Function : Author
Berengere Dadone-Montaudie
  • Function : Author
  • PersonId : 1249336
Estelle Cosson
Julien Guglielmi
  • Function : Author
Thierry Pourcher
Véronique Braud
Institut de pharmacologie moléculaire et cellulaire
Marina Shkreli
Yves-Marie Pers
Christian Jorgensen
Jean-Marc Brondello
Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)
Cellules souches mésenchymateuses, environnement articulaire et immunothérapies de la polyarthrite rhumatoide
Laboratoire de paléontologie et paleogéographie du paleozoique
CV
Chloé Feral
Marie-Cécile Michallet
Centre de Recherche en Cancérologie de Lyon
Eric Gilson
Julien Cherfils-Vicini

Abstract

Although senescent cells can be eliminated by the immune system, they tend to accumulate with age in various tissues. Here we show that senescent cells can evade immune clearance by natural killer (NK) cells by upregulating the expression of the disialylated ganglioside GD3 at their surface. The increased level of GD3 expression on senescent cells that naturally occurs upon aging in liver, lung, kidney or bones leads to a strong suppression of NK-cell-mediated immunosurveillance. In mice, we found that targeting GD3+ senescent cells with anti-GD3 immunotherapy attenuated the development of experimentally induced or age-related lung and liver fibrosis and age-related bone remodeling. These results demonstrate that GD3 upregulation confers immune privilege to senescent cells. We propose that GD3 acts as a senescence immune checkpoint (SIC) that allows senescent cells to escape immunosurveillance and to trigger immune anergy during aging

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Cancer
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Sunday, May 25, 2025

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https://cnrs.hal.science/hal-04802818

Submitted on : Monday, November 25, 2024-3:29:57 PM

Last modification on : Wednesday, January 15, 2025-8:24:47 AM

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hal-04802818 , version 1 (25-11-2024)

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Charlène Iltis, Iryna Moskalevska, Antoine Debiesse, Laetitia Seguin, Christina Fissoun, et al.. A ganglioside-based immune checkpoint enables senescent cells to evade immunosurveillance during aging. Nature Aging, 2024, ⟨10.1101/2021.04.23.440408⟩. ⟨hal-04802818⟩

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