Disruption of cholesterol homeostasis by antidepressants induces immunogenic cell death

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 m...

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Main Authors: Karla Alvarez-Valadez, Jonathan G. Pol, Guido Kroemer, Mojgan Djavaheri-Mergny
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:OncoImmunology
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/2162402X.2025.2531113
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author Karla Alvarez-Valadez
Jonathan G. Pol
Guido Kroemer
Mojgan Djavaheri-Mergny
author_facet Karla Alvarez-Valadez
Jonathan G. Pol
Guido Kroemer
Mojgan Djavaheri-Mergny
author_sort Karla Alvarez-Valadez
collection DOAJ
description 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.
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institution Kabale University
issn 2162-402X
language English
publishDate 2025-12-01
publisher Taylor & Francis Group
record_format Article
series OncoImmunology
spelling doaj-art-cd9cace911574c72bef9cb270e1cc7c62025-08-20T03:50:07ZengTaylor & Francis GroupOncoImmunology2162-402X2025-12-0114110.1080/2162402X.2025.2531113Disruption of cholesterol homeostasis by antidepressants induces immunogenic cell deathKarla Alvarez-Valadez0Jonathan G. Pol1Guido Kroemer2Mojgan Djavaheri-Mergny3Centre de Recherche des Cordeliers, Inserm UMRS 1138, Sorbonne Université, Université de Paris Cité, Équipe labellisée par la Ligue contre le Cancer, Institut Universitaire de France, Paris, FranceCentre de Recherche des Cordeliers, Inserm UMRS 1138, Sorbonne Université, Université de Paris Cité, Équipe labellisée par la Ligue contre le Cancer, Institut Universitaire de France, Paris, FranceCentre de Recherche des Cordeliers, Inserm UMRS 1138, Sorbonne Université, Université de Paris Cité, Équipe labellisée par la Ligue contre le Cancer, Institut Universitaire de France, Paris, FranceCentre de Recherche des Cordeliers, Inserm UMRS 1138, Sorbonne Université, Université de Paris Cité, Équipe labellisée par la Ligue contre le Cancer, Institut Universitaire de France, Paris, FranceSertraline 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.https://www.tandfonline.com/doi/10.1080/2162402X.2025.2531113Antitumor immunitycancercholesterol transportlysosomeserotonin reuptake inhibitors, TFEB
spellingShingle Karla Alvarez-Valadez
Jonathan G. Pol
Guido Kroemer
Mojgan Djavaheri-Mergny
Disruption of cholesterol homeostasis by antidepressants induces immunogenic cell death
OncoImmunology
Antitumor immunity
cancer
cholesterol transport
lysosome
serotonin reuptake inhibitors, TFEB
title Disruption of cholesterol homeostasis by antidepressants induces immunogenic cell death
title_full Disruption of cholesterol homeostasis by antidepressants induces immunogenic cell death
title_fullStr Disruption of cholesterol homeostasis by antidepressants induces immunogenic cell death
title_full_unstemmed Disruption of cholesterol homeostasis by antidepressants induces immunogenic cell death
title_short Disruption of cholesterol homeostasis by antidepressants induces immunogenic cell death
title_sort disruption of cholesterol homeostasis by antidepressants induces immunogenic cell death
topic Antitumor immunity
cancer
cholesterol transport
lysosome
serotonin reuptake inhibitors, TFEB
url https://www.tandfonline.com/doi/10.1080/2162402X.2025.2531113
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AT jonathangpol disruptionofcholesterolhomeostasisbyantidepressantsinducesimmunogeniccelldeath
AT guidokroemer disruptionofcholesterolhomeostasisbyantidepressantsinducesimmunogeniccelldeath
AT mojgandjavaherimergny disruptionofcholesterolhomeostasisbyantidepressantsinducesimmunogeniccelldeath