Role of ferroptosis on tumor progression and immunotherapy

Ferroptosis is triggered by intracellular iron leading to accumulation of lipid peroxidation consequent promotion of cell death. Cancer cell exhibits ability to evade ferroptosis by activation of antioxidant signaling pathways such as SLC7A11/GPX4 axis. In addition to transcriptional regulation on f...

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Published inCell death discovery Vol. 8; no. 1; pp. 427 - 9
Main Authors Gong, Deting, Chen, Mingjun, Wang, Yuhan, Shi, Juanjuan, Hou, Yongzhong
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 26.10.2022
Springer Nature B.V
Nature Publishing Group
Subjects
631/67/580/1884
631/80/474/2073
631/80/82
Antioxidants
Antitumor activity
Apoptosis
Autophagy
Biochemistry
Biomedical and Life Sciences
Breast cancer
Cell Biology
Cell Cycle Analysis
Cell death
Cell survival
Fatty acids
Ferroptosis
Gastric cancer
Gene expression
Gene regulation
Immune checkpoint inhibitors
Immunotherapy
Life Sciences
Lipid peroxidation
Lipids
Lymphocytes T
Macrophages
Protein synthesis
Proteins
Review
Review Article
Stem Cells
Transcription factors
Tumors
Ubiquitination
Yes-associated protein
γ-Interferon
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Summary:Ferroptosis is triggered by intracellular iron leading to accumulation of lipid peroxidation consequent promotion of cell death. Cancer cell exhibits ability to evade ferroptosis by activation of antioxidant signaling pathways such as SLC7A11/GPX4 axis. In addition to transcriptional regulation on ferroptosis by NRF2, SREBP1, YAP, and p53, ferroptosis is modulated by ubiquitination or autophagic degradation. Moreover, zinc or Ca 2+ could modulate ferroptosis by inducing lipid peroxidation and ferroptosis. Induction of ferroptosis enhances immune cell activity such as T cells or macrophages, which is associated with the release of DAMPs (damage-associated molecular patterns) and IFNγ. Therefore, combined immune checkpoint inhibitors with ferroptosis inducers effectively enhance antitumor immunotherapy, whereas induction of ferroptosis could impair T cell activity or survival, suggesting that rational combined therapy for cancer is essential. In this review, we discussed the regulatory role of ferroptosis on tumor progression and immunotherapy.
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ISSN:2058-7716
2058-7716
DOI:10.1038/s41420-022-01218-8