Antitumor T‐cell function requires CPEB4‐mediated adaptation to chronic endoplasmic reticulum stress

Abstract: Tumor growth is influenced by a complex network of interactions between multiple cell types in the tumor microenvironment (TME). These constrained conditions trigger the endoplasmic reticulum (ER) stress response, which extensively reprograms mRNA translation. When uncontrolled over time, chronic ER stress impairs the antitumor effector function of CD8 T lymphocytes. How cells promote adaptation to chronic stress in the TME without the detrimental effects of the terminal unfolded protein response (UPR) is unknown. Here, we find that, in effector CD8 T lymphocytes, RNA‐binding protein CPEB4 constitutes a new branch of the UPR that allows cells to adapt to sustained ER stress, yet remains decoupled from the terminal UPR. ER stress, induced during CD8 T‐cell activation and effector function, triggers CPEB4 expression. CPEB4 then mediates chronic stress adaptation to maintain cellular fitness, allowing effector molecule production and cytotoxic activity. Accordingly, this branch of the UPR is required for the antitumor effector function of T lymphocytes, and its disruption in these cells exacerbates tumor growth.

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch

Bibliographic citation
Antitumor T‐cell function requires CPEB4‐mediated adaptation to chronic endoplasmic reticulum stress ; day:15 ; month:03 ; year:2023 ; extent:14
The EMBO journal / European Molecular Biology Organization ; (15.03.2023) (gesamt 14)

Creator
Fernández‐Alfara, Marcos
Sibilio, Annarita
Martin, Judit
Tusquets Uxó, Elsa
Malumbres, Marina
Alcalde, Victor
Chanes, Verónica
Cañellas‐Socias, Adrià
Palomo‐Ponce, Sergio
Batlle, Eduard
Méndez, Raúl

DOI
10.15252/embj.2022111494
URN
urn:nbn:de:101:1-2023031514354002467800
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
14.08.2025, 10:46 AM CEST

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Associated

  • Fernández‐Alfara, Marcos
  • Sibilio, Annarita
  • Martin, Judit
  • Tusquets Uxó, Elsa
  • Malumbres, Marina
  • Alcalde, Victor
  • Chanes, Verónica
  • Cañellas‐Socias, Adrià
  • Palomo‐Ponce, Sergio
  • Batlle, Eduard
  • Méndez, Raúl

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