A review of the participation of DDIT4 in the tumor immune microenvironment through inhibiting PI3K-Akt/mTOR pathway

DDIT4 (DNA Damage Inducible Transcript 4), a well-established inhibitor of the PI3K-Akt/mTOR pathway, is upregulated under cellular stress conditions. Extensive research has demonstrated that DDIT4 expression is aberrantly elevated in various malignancies, where it exhibits context-dependent roles i...

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Main Authors: Yunshu Jiao, Yang Xiang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1595463/full
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author Yunshu Jiao
Yang Xiang
author_facet Yunshu Jiao
Yang Xiang
author_sort Yunshu Jiao
collection DOAJ
description DDIT4 (DNA Damage Inducible Transcript 4), a well-established inhibitor of the PI3K-Akt/mTOR pathway, is upregulated under cellular stress conditions. Extensive research has demonstrated that DDIT4 expression is aberrantly elevated in various malignancies, where it exhibits context-dependent roles in either tumor promotion or suppression. However, the mechanisms underlying how DDIT4 is involved in tumor immune regulation remain to be fully elucidated. This review systematically summarizes the multifaceted mechanisms by which DDIT4 participates in tumor immunomodulation, primarily through its inhibition of the PI3K-Akt/mTOR pathway to induce autophagy activation and metabolic reprogramming; furthermore, it comprehensively examines DDIT4’s regulatory effects on various components within the tumor immune microenvironment, including tumor cells, both innate and adaptive immune cells, and immunomodulatory cytokines. This comprehensive analysis aims to establish a theoretical foundation for considering DDIT4 as a potential therapeutic target in tumor immunotherapy.
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publishDate 2025-08-01
publisher Frontiers Media S.A.
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series Frontiers in Oncology
spelling doaj-art-e9da465e40064b6d9b18055d22639f702025-08-20T03:46:45ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-08-011510.3389/fonc.2025.15954631595463A review of the participation of DDIT4 in the tumor immune microenvironment through inhibiting PI3K-Akt/mTOR pathwayYunshu Jiao0Yang Xiang1Clinical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDDIT4 (DNA Damage Inducible Transcript 4), a well-established inhibitor of the PI3K-Akt/mTOR pathway, is upregulated under cellular stress conditions. Extensive research has demonstrated that DDIT4 expression is aberrantly elevated in various malignancies, where it exhibits context-dependent roles in either tumor promotion or suppression. However, the mechanisms underlying how DDIT4 is involved in tumor immune regulation remain to be fully elucidated. This review systematically summarizes the multifaceted mechanisms by which DDIT4 participates in tumor immunomodulation, primarily through its inhibition of the PI3K-Akt/mTOR pathway to induce autophagy activation and metabolic reprogramming; furthermore, it comprehensively examines DDIT4’s regulatory effects on various components within the tumor immune microenvironment, including tumor cells, both innate and adaptive immune cells, and immunomodulatory cytokines. This comprehensive analysis aims to establish a theoretical foundation for considering DDIT4 as a potential therapeutic target in tumor immunotherapy.https://www.frontiersin.org/articles/10.3389/fonc.2025.1595463/fullDDIT4mTORC1tumor immune microenvironmentautophagyPI3K-Akt/mTOR pathway
spellingShingle Yunshu Jiao
Yang Xiang
A review of the participation of DDIT4 in the tumor immune microenvironment through inhibiting PI3K-Akt/mTOR pathway
Frontiers in Oncology
DDIT4
mTORC1
tumor immune microenvironment
autophagy
PI3K-Akt/mTOR pathway
title A review of the participation of DDIT4 in the tumor immune microenvironment through inhibiting PI3K-Akt/mTOR pathway
title_full A review of the participation of DDIT4 in the tumor immune microenvironment through inhibiting PI3K-Akt/mTOR pathway
title_fullStr A review of the participation of DDIT4 in the tumor immune microenvironment through inhibiting PI3K-Akt/mTOR pathway
title_full_unstemmed A review of the participation of DDIT4 in the tumor immune microenvironment through inhibiting PI3K-Akt/mTOR pathway
title_short A review of the participation of DDIT4 in the tumor immune microenvironment through inhibiting PI3K-Akt/mTOR pathway
title_sort review of the participation of ddit4 in the tumor immune microenvironment through inhibiting pi3k akt mtor pathway
topic DDIT4
mTORC1
tumor immune microenvironment
autophagy
PI3K-Akt/mTOR pathway
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1595463/full
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