Ferroptosis in cancer and cancer immunotherapy

Zhao, Lei; Zhou, Xiaoxue; Xie, Feng; Zhang, Lei; Yan, Haiyan; Huang, Jun; Zhang, Chong; Zhou, Fangfang; Chen, Jun; Zhang, Long

doi:10.1002/cac2.12250

Cited by 295 publications

(188 citation statements)

References 238 publications

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“…NCOA4 overexpression leads to the generation of excess free iron and ferroptosis through Fenton reactions, which can be rescued by ferrostatin-1. 55 …”

Section: Discussionmentioning

confidence: 99%

NCOA4-Mediated Ferroptosis in Bronchial Epithelial Cells Promotes Macrophage M2 Polarization in COPD Emphysema

Liu¹,

Zhang²,

Yang³

et al. 2022

COPD

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Background Macrophage polarization plays an important role in the pathogenesis of COPD emphysema. Changes in macrophage polarization in COPD remain unclear, while polarization and ferroptosis are essential factors in its pathogenesis. Therefore, this study investigated the relationship between macrophage polarization and ferroptosis in COPD emphysema. Methods We measured macrophage polarization and the levels of matrix metalloproteinases (MMPs) in the lung tissues of COPD patients and cigarette smoke (CS)-exposed mice. Flow cytometry was used to determine macrophage (THP-M cell) polarization changes. Ferroptosis was examined by FerroOrange, Perls’ DAB, C11-BODIPY and 4-HNE staining. Nuclear receptor coactivator 4 (NCOA4) was measured in the lung tissues of COPD patients and CS-exposed mice by western blotting. A cell study was performed to confirm the regulatory effect of NCOA4 on macrophage polarization. Results Increased M2 macrophages and MMP9 and MMP12 levels were observed in COPD patients, CS-exposed mice and THP-M cells cocultured with CS extract (CSE)-treated human bronchial epithelial (HBE) cells. Increased NCOA4 levels and ferroptosis were confirmed in COPD. Treatment with NCOA4 siRNA and the ferroptosis inhibitor ferrostatin-1 revealed an association between ferroptosis and M2 macrophages. These findings support a role for NCOA4, which induces an increase in M2 macrophages, in the pathogenesis of COPD emphysema. Conclusion In our study, CS led to the dominance of the M2 phenotype in COPD. We identified NCOA4 as a regulator of M2 macrophages and emphysema by mediating ferroptosis, which offers a new direction for research into COPD diagnostics and treatment.

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“…NCOA4 overexpression leads to the generation of excess free iron and ferroptosis through Fenton reactions, which can be rescued by ferrostatin-1. 55 …”

Section: Discussionmentioning

confidence: 99%

NCOA4-Mediated Ferroptosis in Bronchial Epithelial Cells Promotes Macrophage M2 Polarization in COPD Emphysema

Liu¹,

Zhang²,

Yang³

et al. 2022

COPD

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“…Lipids and lipogenesis have been associated with several ailments [ 11 – 14 ]. Western medicine uses lipid-lowering drugs to stabilize plaques, but removing the plaques has shown controversial results as the drugs used may have a short half-life and significant adverse events [ 15 – 17 ].…”

Section: Introductionmentioning

confidence: 99%

Acupuncture Combined with Traditional Chinese Medicine and Drug Therapy for the Treatment of Cerebral Infarction (Phlegm-Blood Stasis Syndrome) and Carotid Atherosclerotic Plaque: A Preliminary Randomized Controlled Study

Wang

Liu

2022

Applied Bionics and Biomechanics

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Carotid atherosclerotic plaque (CAP) is one of the leading causes of cerebral infarction. Western medicine usually uses lipid-lowering drugs to stabilize plaques. Currently, studies reporting on drugs that can reduce plaques are lacking. Here, we performed a randomized controlled study to investigate the effectiveness of acupuncture combined with drug therapy (TCM and Western) to treat cerebral infarction (phlegm-blood stasis syndrome) and CAP. The control group was treated with atorvastatin calcium tablets (20 mg/d, po for 15 days). The treatment group received atorvastatin calcium tablets 20 mg, traditional Chinese medicine (TCM) decoctions (two matured substance decoction plus peach kernel and Carthamus four substance decoction plus Chinese hawthorn fruit 20 g, gold theragran 20 g, and red yeast rice 3 g), and acupuncture therapy, once daily for 15 days as one treatment course. The patients’ neurological deficit score, ultrasonic testing of the carotid artery, and lipoprotein-associated phospholipase A2 (Lp-PLA2) were evaluated. Our findings showed no significant difference in the evaluated indices between the two groups before treatment ( P > 0.05 ). However, compared with the control group after 15 days of treatment and within each group before and after treatment, the differences were significant ( P < 0.05 ). In conclusion, acupuncture combined with drug therapy demonstrated promising effectiveness in treating cerebral infarction (phlegm-blood stasis syndrome) and CAP.

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“…The subsequent oxidative damage and oxidative stress imbalance induced by ferroptosis contribute to cell death in multiple cancer cells ( Bebber et al, 2020 ; Chen X. et al, 2021 ). In fact, initiating ferroptosis pathways may be able to overcome existing chemotherapeutic resistance and open a new therapeutic area for cancer treatment ( Zhao et al, 2022 ). Therefore, understanding the molecular mechanism of ferroptosis in HCC is a promising therapeutic strategy for liver cancer that selectively induces ferroptosis.…”

Section: Discussionmentioning

confidence: 99%

Development and Validation of a Novel Ferroptosis-Related Gene Signature for Prognosis and Immunotherapy in Hepatocellular Carcinoma

Zhang

Zhao

Liu

et al. 2022

Front. Mol. Biosci.

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Hepatocellular carcinoma (HCC) is a cancer that is sensitive to ferroptosis, and immunotherapy has emerged as a promising treatment for HCC patients. However, the prognostic potential of ferroptosis-related genes (FRGs) and the effect of ferroptosis on the tumor immune microenvironment in HCC remain largely obscure. Here, we analyzed the expression pattern of FRGs using the TCGA, ICGC and GEO databases. The expression of most FRGs was upregulated in HCC tissues compared with normal liver tissues. Three independent clusters were determined by consensus clustering analysis based on FRG expression in HCC. Cluster 3 exhibited higher expression, unfavorable prognosis, and higher histological tumor stage and grade than clusters 1 and 2. CIBERSORT analysis indicated different infiltrating levels of various immune cells among the three clusters. Moreover, most immune checkpoint genes were highly expressed in cluster 3. Univariate Cox regression and LASSO regression analyses were performed to develop a five FRG-based prognostic risk model using the TCGA and ICGC datasets. Kaplan–Meier analysis and ROC curves were performed to verify the prognostic potential of the risk model. A nomogram containing independent prognostic factors was further developed. Compared with low-risk patients, high-risk HCC patients exhibited worse overall survival (OS). In addition, this risk model was significantly correlated with the infiltrating levels of six major types of immune cells in HCC. Finally, the relationships between the five FRGs and drug sensitivity were investigated. The present study suggests that the five FRGs could elucidate the molecular mechanisms of HCC and lead to a new direction for the improvement of predictive, preventive, and personalized medicine for HCC.

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Ferroptosis in cancer and cancer immunotherapy

Cited by 295 publications

References 238 publications

NCOA4-Mediated Ferroptosis in Bronchial Epithelial Cells Promotes Macrophage M2 Polarization in COPD Emphysema

NCOA4-Mediated Ferroptosis in Bronchial Epithelial Cells Promotes Macrophage M2 Polarization in COPD Emphysema

Acupuncture Combined with Traditional Chinese Medicine and Drug Therapy for the Treatment of Cerebral Infarction (Phlegm-Blood Stasis Syndrome) and Carotid Atherosclerotic Plaque: A Preliminary Randomized Controlled Study

Development and Validation of a Novel Ferroptosis-Related Gene Signature for Prognosis and Immunotherapy in Hepatocellular Carcinoma

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