Disruption of cholesterol homeostasis by antidepressants induces immunogenic cell death

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Abstract
Sertraline and indatraline are two antidepressants that function as serotonin reuptake inhibitors and have demonstrated promising anticancer potential, although their precise mechanisms of action remain unclear. Both compounds trigger cholesterol accumulation within lysosomes followed by lysosomal membrane permeabilization, ultimately leading to the activation of immunogenic cell death (ICD). This, in turn, triggers a T cell-mediated adaptive immune response that facilitates significant tumor control.
Funding Information
  • INCA PLBIO (PLBIO23-216-2023-181)
  • Mexican National Council of Science and Technology (CONACYT)
  • Mexican National Council of Science and Technology (funding#757821)
  • Ligue Contre le Cancer (IP/SC-17519)
  • Institut National de la Santé et de laRecherche Médicale (PLBIO23-216-2023-181)
  • Ligue Contre le Cancer
  • Agence national de la recherche (ANR-22-CE14-0066 VIVORUSH)
  • Agence national de la recherche (ANR-23-CE44-0030 COPPERMAC)
  • Agence national de la recherche (ANR-23-R4HC-0006 Ener-LIGHT)
  • Association pour la Recherche sur le Cancer
  • CancéropôleIle-de-France
  • Fondation pour la Recherche Médicale
  • European Research Council Advanced Investigator (101052444)
  • project acronym: ICD-Cancer
  • project title: Immunogenic cell death (ICD) in the cancer-immune dialogue
  • European Union Horizon 2020 research and innovation programs (825410)
  • ONCOBIOME, Project title: Gut OncoMicrobiome Signatures [GOMS] associated with cancer incidence (101095604)
  • Agence Nationale de la Recherche (21-ESRE-0028)
  • Institut National Du Cancer
  • RHUs Immunolife and LUCA-pi (ANR-21-RHUS-0017)
  • SeeraveFoundation
  • IdEx Université de Paris Cité (ANR-18-IDEX-0001)

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