ArticleCell death and differentiation2024
Phospholipid peroxidation in macrophage confers tumor resistance by suppressing phagocytic capability towards ferroptotic cells.
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Article in Cell death and differentiation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21citing papers in PubMed
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Who cites it
21 citing papers in PubMed.
- Ferroptosis-driven immune remodeling in heart failure: the central role of macrophage reprogramming and impaired efferocytosis.Journal of nanobiotechnology · 2026Review
- Ferroptosis and macrophage polarization: mechanisms, interplay, and implications for medical applications.Cell death discovery · 2026Review
- Ferroptosis as a Pathogenic Mechanism and Therapeutic Target in Autoimmune and Inflammatory Skin Diseases.Clinical reviews in allergy & immunology · 2026Review
- The controversial role of metabolic reprogramming in anti-tumor therapy resistance.Discover oncology · 2026Review
- Bidirectional regulation between ferroptosis and tumor-associated macrophages: mechanisms, strategies, and therapeutic perspectives.Frontiers in oncology · 2026Review
- The Role of Lipid Metabolism in the Progression of Breast Cancer.Journal of Cancer · 2026Review
- Advances in ferroptosis mechanisms and therapeutic potential in head and neck squamous cell carcinoma.Frontiers in cell and developmental biology · 2026Review
- Remodeling the tumor immune microenvironment: mechanisms of crosstalk between regulated cell death macrophages.Frontiers in immunology · 2026Review
- Copper-Iron Cell Death Axis: Mechanistic Crosstalk, Disease Implications and an Integrated Metallo-Redox-Metabolic Framework.International journal of biological sciences · 2026Review
- Ferroptosis reshapes the tumor immune microenvironment: molecular mechanisms, immune regulation, and therapeutic synergistic strategies.Frontiers in immunology · 2026Review
- Iron-Driven Ferroptosis in Diabetic Kidney Disease: From Molecular Mechanisms to Targeted Therapeutic Translation.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Ganoderma lucidum spore oil alleviates psychological stress-evoked tumor progression by enhancing FcγR-mediated macrophage phagocytosis.Chinese medicine · 2025Article
- "Weibing" in traditional Chinese medicine-biological basis and mathematical representation of disease-susceptible state.Acta pharmaceutica Sinica. B · 2025Review
- Lipotoxicity, lipid peroxidation and ferroptosis: a dilemma in cancer therapy.Cell biology and toxicology · 2025Review
- CNPY3's regulation of tumor microenvironment and its impact on colon cancer aggressiveness.Molecular medicine (Cambridge, Mass.) · 2025Article
- Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets.Signal transduction and targeted therapy · 2025Review
- The role of canopy family proteins: biological mechanism and disease function.Molecular biology reports · 2025Review
- New functions of oxylipins released by pyroptotic cells.Acta pharmaceutica Sinica. B · 2024Article
- Ferroptosis and the tumor microenvironment.Journal of experimental & clinical cancer research : CR · 2024Review
- Ferroptosis as a new tool for tumor suppression through lipid peroxidation.Communications biology · 2024Review
Corrections and comments
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Authors and funding
22 authors.
Xiang Luo *Guangdong Second Provincial General Hospital/Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility/Guangzhou Key Laboratory of Traditional Chinese Medicine & Disease Susceptibility/Guangdong-Hong Kong-Macao Universities Joint Laboratory for the Internationalization of Traditional Chinese Medicine/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/State Key Laboratory of Bioactive Molecules and Druggability Assessment/Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, 510632, China.
Hai-Biao Gong *Guangdong Second Provincial General Hospital/Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility/Guangzhou Key Laboratory of Traditional Chinese Medicine & Disease Susceptibility/Guangdong-Hong Kong-Macao Universities Joint Laboratory for the Internationalization of Traditional Chinese Medicine/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/State Key Laboratory of Bioactive Molecules and Druggability Assessment/Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, 510632, China.ORCID 0000-0001-7343-6866
Zi-Chun LiGuangdong Second Provincial General Hospital/Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility/Guangzhou Key Laboratory of Traditional Chinese Medicine & Disease Susceptibility/Guangdong-Hong Kong-Macao Universities Joint Laboratory for the Internationalization of Traditional Chinese Medicine/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/State Key Laboratory of Bioactive Molecules and Druggability Assessment/Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, 510632, China.
Dong-Dong LiGuangdong Second Provincial General Hospital/Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility/Guangzhou Key Laboratory of Traditional Chinese Medicine & Disease Susceptibility/Guangdong-Hong Kong-Macao Universities Joint Laboratory for the Internationalization of Traditional Chinese Medicine/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/State Key Laboratory of Bioactive Molecules and Druggability Assessment/Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, 510632, China.
Zi-Xuan LiGuangdong Second Provincial General Hospital/Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility/Guangzhou Key Laboratory of Traditional Chinese Medicine & Disease Susceptibility/Guangdong-Hong Kong-Macao Universities Joint Laboratory for the Internationalization of Traditional Chinese Medicine/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/State Key Laboratory of Bioactive Molecules and Druggability Assessment/Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, 510632, China.
Jie SunGuangdong Second Provincial General Hospital/Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility/Guangzhou Key Laboratory of Traditional Chinese Medicine & Disease Susceptibility/Guangdong-Hong Kong-Macao Universities Joint Laboratory for the Internationalization of Traditional Chinese Medicine/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/State Key Laboratory of Bioactive Molecules and Druggability Assessment/Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, 510632, China.
Chang-Yu YanGuangdong Second Provincial General Hospital/Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility/Guangzhou Key Laboratory of Traditional Chinese Medicine & Disease Susceptibility/Guangdong-Hong Kong-Macao Universities Joint Laboratory for the Internationalization of Traditional Chinese Medicine/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/State Key Laboratory of Bioactive Molecules and Druggability Assessment/Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, 510632, China.
Rui-Ting HuangState Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, 999078, China.
Yue FengDepartment of Materials Science and Engineering, College of Chemistry and Materials Science, Jinan University, Guangzhou, 511443, China.
Shu-Rui ChenGuangdong Second Provincial General Hospital/Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility/Guangzhou Key Laboratory of Traditional Chinese Medicine & Disease Susceptibility/Guangdong-Hong Kong-Macao Universities Joint Laboratory for the Internationalization of Traditional Chinese Medicine/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/State Key Laboratory of Bioactive Molecules and Druggability Assessment/Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, 510632, China.
Yun-Feng CaoShanghai Institute for Biomedical and Pharmaceutical Technologies, National Health Commission Key Laboratory of Reproduction Regulation, Shanghai, China.
Mingxian LiuDepartment of Materials Science and Engineering, College of Chemistry and Materials Science, Jinan University, Guangzhou, 511443, China.
Rong WangGuangdong Second Provincial General Hospital/Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility/Guangzhou Key Laboratory of Traditional Chinese Medicine & Disease Susceptibility/Guangdong-Hong Kong-Macao Universities Joint Laboratory for the Internationalization of Traditional Chinese Medicine/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/State Key Laboratory of Bioactive Molecules and Druggability Assessment/Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, 510632, China.
Feng HuangSchool of Chinese Materia Medica and Yunnan Key Laboratory of Southern Medicinal Utilization, Yunnan University of Chinese Medicine, Kunming, 650500, China.
Wan-Yang SunGuangdong Second Provincial General Hospital/Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility/Guangzhou Key Laboratory of Traditional Chinese Medicine & Disease Susceptibility/Guangdong-Hong Kong-Macao Universities Joint Laboratory for the Internationalization of Traditional Chinese Medicine/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/State Key Laboratory of Bioactive Molecules and Druggability Assessment/Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, 510632, China.ORCID 0000-0002-4439-967X
Hiroshi KuriharaGuangdong Second Provincial General Hospital/Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility/Guangzhou Key Laboratory of Traditional Chinese Medicine & Disease Susceptibility/Guangdong-Hong Kong-Macao Universities Joint Laboratory for the Internationalization of Traditional Chinese Medicine/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/State Key Laboratory of Bioactive Molecules and Druggability Assessment/Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, 510632, China.
Wen-Jun DuanGuangdong Second Provincial General Hospital/Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility/Guangzhou Key Laboratory of Traditional Chinese Medicine & Disease Susceptibility/Guangdong-Hong Kong-Macao Universities Joint Laboratory for the Internationalization of Traditional Chinese Medicine/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/State Key Laboratory of Bioactive Molecules and Druggability Assessment/Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, 510632, China.ORCID 0000-0001-7324-9526
Lei LiangGuangdong Second Provincial General Hospital/Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility/Guangzhou Key Laboratory of Traditional Chinese Medicine & Disease Susceptibility/Guangdong-Hong Kong-Macao Universities Joint Laboratory for the Internationalization of Traditional Chinese Medicine/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/State Key Laboratory of Bioactive Molecules and Druggability Assessment/Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, 510632, China.
Wen JinGuangdong Second Provincial General Hospital/Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility/Guangzhou Key Laboratory of Traditional Chinese Medicine & Disease Susceptibility/Guangdong-Hong Kong-Macao Universities Joint Laboratory for the Internationalization of Traditional Chinese Medicine/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/State Key Laboratory of Bioactive Molecules and Druggability Assessment/Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, 510632, China.
Yan-Ping WuGuangdong Second Provincial General Hospital/Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility/Guangzhou Key Laboratory of Traditional Chinese Medicine & Disease Susceptibility/Guangdong-Hong Kong-Macao Universities Joint Laboratory for the Internationalization of Traditional Chinese Medicine/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/State Key Laboratory of Bioactive Molecules and Druggability Assessment/Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, 510632, China. wuyanping@jnu.edu.cn.ORCID 0009-0008-2114-4755
Rong-Rong HeGuangdong Second Provincial General Hospital/Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility/Guangzhou Key Laboratory of Traditional Chinese Medicine & Disease Susceptibility/Guangdong-Hong Kong-Macao Universities Joint Laboratory for the Internationalization of Traditional Chinese Medicine/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/State Key Laboratory of Bioactive Molecules and Druggability Assessment/Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, 510632, China. rongronghe@jnu.edu.cn.ORCID 0000-0001-5505-5672
Yi-Fang LiGuangdong Second Provincial General Hospital/Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility/Guangzhou Key Laboratory of Traditional Chinese Medicine & Disease Susceptibility/Guangdong-Hong Kong-Macao Universities Joint Laboratory for the Internationalization of Traditional Chinese Medicine/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE)/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/State Key Laboratory of Bioactive Molecules and Druggability Assessment/Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, 510632, China. liyifang706@jnu.edu.cn.ORCID 0000-0002-3356-3702
Funding
China Postdoctoral Science Foundation 2022TQ0122China Postdoctoral Science Foundation 2023M731327Medical Science and Technology Foundation of Guangdong Province (Science and Technology Foundation of Guangdong Province) A2023044National Natural Science Foundation of China (National Science Foundation of China) 81903821National Natural Science Foundation of China (National Science Foundation of China) 81973718National Natural Science Foundation of China (National Science Foundation of China) 82004231National Natural Science Foundation of China (National Science Foundation of China) 82125038National Natural Science Foundation of China (National Science Foundation of China) 82274403National Natural Science Foundation of China (National Science Foundation of China) T2341004National Outstanding Youth Foundation of China 82305063Natural Science Foundation of Guangdong Province (Guangdong Natural Science Foundation) 2020A1515110388Natural Science Foundation of Guangdong Province (Guangdong Natural Science Foundation) 2021A1515011297Natural Science Foundation of Guangdong Province (Guangdong Natural Science Foundation) 2021B1515120023Natural Science Foundation of Guangdong Province (Guangdong Natural Science Foundation) 2023B1515040016
Abstract
Ferroptosis holds significant potential for application in cancer therapy. However, ferroptosis inducers are not cell-specific and can cause phospholipid peroxidation in both tumor and non-tumor cells. This limitation greatly restricts the use of ferroptosis therapy as a safe and effective anticancer strategy. Our previous study demonstrated that macrophages can engulf ferroptotic cells through Toll-like receptor 2 (TLR2). Despite this advancement, the precise mechanism by which phospholipid peroxidation in macrophages affects their phagocytotic capability during treatment of tumors with ferroptotic agents is still unknown. Here, we utilized flow sorting combined with redox phospholipidomics to determine that phospholipid peroxidation in tumor microenvironment (TME) macrophages impaired the macrophages ability to eliminate ferroptotic tumor cells by phagocytosis, ultimately fostering tumor resistance to ferroptosis therapy. Mechanistically, the accumulation of phospholipid peroxidation in the macrophage endoplasmic reticulum (ER) repressed TLR2 trafficking to the plasma membrane and caused its retention in the ER by disrupting the interaction between TLR2 and its chaperone CNPY3. Subsequently, this ER-retained TLR2 recruited E3 ligase MARCH6 and initiated the proteasome-dependent degradation. Using redox phospholipidomics, we identified 1-steaoryl-2-15-HpETE-sn-glycero-3-phosphatidylethanolamine (SAPE-OOH) as the crucial mediator of these effects. Conclusively, our discovery elucidates a novel molecular mechanism underlying macrophage phospholipid peroxidation-induced tumor resistance to ferroptosis therapy and highlights the TLR2-MARCH6 axis as a potential therapeutic target for cancer therapy.
Indexed as
FerroptosisLipid PeroxidationMacrophagesPhagocytosisPhospholipidsAnimalsCell Line, TumorHumansMiceMice, Inbred C57BLNeoplasmsRAW 264.7 CellsToll-Like Receptor 2Tumor MicroenvironmentPhospholipidsToll-Like Receptor 2
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.