Ferroptosis: A Critical Moderator in the Life Cycle of Immune Cells

Wang, Ping; Lu, Yuan-Qiang

doi:10.3389/fimmu.2022.877634

Cited by 27 publications

(27 citation statements)

References 84 publications

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“…We found that patients with high ferroptosis scores experienced longer survival time. CD8 + T cells can induce ferroptosis in tumor cells, and then improve the anti-tumor effect (23). Consistently, our GSEA results showed that there was signi cant activation of immune-related pathway in ferroptosis score high group, indicating that ferroptosis may affect the prognosis through these immune pathways.…”

Section: Discussionsupporting

confidence: 81%

Novel Ferroptosis-related gene signature for predicting the prognosis of breast cancer

Guo

Cui

et al. 2022

Preprint

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Background: Ferroptosis is a novel form of regulated cell death, however, the potential functions of ferroptosis in the breast cancer (BRCA) prognosis, immune infiltration, and drug resistance remain unknown. Methods: In this study, the characteristic patterns of ferroptosis in estrogen receptor–positive (ER+) breast cancer were systematically investigated with the interactions between ferroptosis and the tumor microenvironment (TME). On the mRNA expression profiles of 56 ferroptosis-related genes (FRGs), two ferroptosis patterns were constructed, with distinct prognosis, immune cell infiltrations and tamoxifen resistance. Results: The high ferroptosis scores were characterized by better prognosis, increased immune cell infiltration, higher immune and stromal scores, lower tumor purity, lower tumor mutational burden (TMB) and better Tamoxifen response, immune-related pathways showed statistically significant activation, while pathways related to cell repair and metabolism showed significant inhibition. Conclusion: Collectively, ferroptosis could be involved in the diverse and complex TME. Evaluation of the ferroptosis patterns may heighten the comprehension about immune infiltrations in the TME, ferroptosis-related risk score model can predict the prognostic of ER + BRCA patients and for the treatment of resistance to tamoxifen administration and assisting oncologists to generate individualized immunotherapeutic strategies.

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Section: Discussionsupporting

confidence: 81%

Novel Ferroptosis-related gene signature for predicting the prognosis of breast cancer

Guo

Cui

et al. 2022

Preprint

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“…On the one hand, the ferroptosis of immune cells reduce their number and function, impairing the immune response. On the other side, the ferroptosis of non-immune cells will cause the release of damage-associated molecular pattern (DAMP) and trigger immune responses ( Wang and Lu, 2022 ). Zou et al ( Wang et al, 2019 ) found that IFN γ derived from immunotherapy-activated CD8 + T cells could down-regulate SLC3A2 and SLC7A11 levels, leading to decreased cystine uptake and enhanced tumor lipid oxidation and ferroptosis.…”

Section: The Role Of Ferroptosis In Tumorsmentioning

confidence: 99%

Cooperation effects of radiation and ferroptosis on tumor suppression and radiation injury

Bian²,

Zheng³

et al. 2022

Front. Cell Dev. Biol.

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Ferroptosis is a kind of oxidative stress-dependent cell death characterized by iron accumulation and lipid peroxidation. It can work in conjunction with radiation to increase reactive oxygen species (ROS) generation and disrupt the antioxidant system, suppressing tumor progression. Radiation can induce ferroptosis by creating ROS, depleting glutathione, activating genes linked to DNA damage and increasing the expression of acyl-CoA synthetase long-chain family member 4 (ACSL4) in tumor cells. Furthermore, ferroptosis can enhance radiosensitivity by causing an iron overload, destruction of the antioxidant system, and lipid peroxidation. Radiation can also cause ferroptosis in normal cells, resulting in radiation injury. The role of ferroptosis in radiation-induced lung, intestinal, skin, and hematological injuries have been studied. In this review, we summarize the potential mechanisms linking ferroptosis, oxidative stress and radiation; analyze the function of ferroptosis in tumor suppression and radiation injury; and discuss the potential of ferroptosis regulation to improve radiotherapy efficacy and reduce adverse effects.

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“…Studies have revealed that ferroptosis plays a direct role in the immune response, and that immune cells undergo ferroptosis under specific conditions, causing impaired immune activity [ 45 ]. These facts, combined with our work, lead us to believe that immune cell ferroptosis increased in Per1/Per2 DKO mice in old age (14 months), and is responsible for the decreases in immune cell numbers, affecting the spleen’s immune function in mice.…”

Section: Discussionmentioning

confidence: 99%

Per1/Per2 knockout Affects Spleen Immune Function in Elderly Mice via Inducing Spleen Lymphocyte Ferroptosis

Zhang

et al. 2022

IJMS

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Disturbances in circadian rhythms are known to affect immune functions. However, the long-term impact of abnormal circadian rhythms on the immune-related functions of the spleen are poorly understood. Hence, we aimed to investigate the immune-related functions of spleen in Per1/Per2 double-knockout (DKO) and wild-type (WT) mice aged 4, 9, and 14 months. Compared to the WT mice, the DKO mice had smaller spleen white pulp (WP) and lymphocyte germinal area, as well as fewer immune cells with age—these differences were especially clear. The spleen lymphocyte mortality, malondialdehyde (MDA) levels, reactive oxygen species (ROS) levels, and ferritin-binding receptor (TFR1) levels were significantly higher in the 14-month-old DKO mice than in WT mice of the same age. Transcriptome analysis showed that most of the differentially expressed mRNAs were enriched in DNA damage repair-related pathways. In DKO mice, spleen cells showed up-regulation of pro-ferroptosis genes, such as Cd36, Atm, and Acsl4, and down-regulation of anti-ferroptosis genes, such as GPX4. We found that long-term abnormalities in the circadian rhythm can induce DNA damage and ferroptosis in mouse spleen.

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Ferroptosis: A Critical Moderator in the Life Cycle of Immune Cells

Cited by 27 publications

References 84 publications

Novel Ferroptosis-related gene signature for predicting the prognosis of breast cancer

Novel Ferroptosis-related gene signature for predicting the prognosis of breast cancer

Cooperation effects of radiation and ferroptosis on tumor suppression and radiation injury

Per1/Per2 knockout Affects Spleen Immune Function in Elderly Mice via Inducing Spleen Lymphocyte Ferroptosis

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