Iron-mediated ferroptosis impairs CAR-T cell function and antitumor efficacy

Zhang, J. et al. Non-viral, specifically targeted CAR-T cells achieve high safety and efficacy in B-NHL. Nature 609, 369–374 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sterner, R. C. & Sterner, R. M. CAR-T cell therapy: current limitations and potential strategies. Blood Cancer J. 11, 69 (2021).

Article  PubMed  PubMed Central  Google Scholar 

Cappell, K. M. & Kochenderfer, J. N. Long-term outcomes following CAR T cell therapy: what we know so far. Nat. Rev. Clin. Oncol. 20, 359–371 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Abou-El-Enein, M. et al. Scalable manufacturing of CAR T cells for cancer immunotherapy. Blood Cancer Discov. 2, 408–422 (2021).

Article  CAS  PubMed  Google Scholar 

Wang, D. et al. CRISPR screening of CAR T cells and cancer stem cells reveals critical dependencies for cell-based therapies. Cancer Discov. 11, 1192–1211 (2021).

Article  CAS  PubMed  Google Scholar 

Dufva, O. et al. Integrated drug profiling and CRISPR screening identify essential pathways for CAR T-cell cytotoxicity. Blood 135, 597–609 (2020).

Article  PubMed  PubMed Central  Google Scholar 

Sprent, J. & Tough, D. F. T cell death and memory. Science 293, 245–248 (2001).

Article  CAS  PubMed  Google Scholar 

Spetz, J., Presser, A. G. & Sarosiek, K. A. T cells and regulated cell death: kill or be killed. Int. Rev. Cell Mol. Biol. 342, 27–71 (2019).

Article  CAS  PubMed  Google Scholar 

Tang, R. et al. Ferroptosis, necroptosis, and pyroptosis in anticancer immunity. J. Hematol. Oncol. 13, 110 (2020).

Article  PubMed  PubMed Central  Google Scholar 

Voss, K. et al. Elevated transferrin receptor impairs T cell metabolism and function in systemic lupus erythematosus. Sci Immunol 8, eabq0178 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jiang, X., Stockwell, B. R. & Conrad, M. Ferroptosis: mechanisms, biology and role in disease. Nat. Rev. Mol. Cell Biol. 22, 266–282 (2021).

Article  PubMed  PubMed Central  Google Scholar 

Teh, M. R., Frost, J. N., Armitage, A. E. & Drakesmith, H. Analysis of iron and iron-interacting protein dynamics during T-cell activation. Front. Immunol. 12, 714613 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yao, Y. et al. Selenium–GPX4 axis protects follicular helper T cells from ferroptosis. Nat. Immunol. 22, 1127–1139 (2021).

Article  CAS  PubMed  Google Scholar 

Zhang, M. et al. Risk factors associated with durable progression-free survival in patients with relapsed or refractory multiple myeloma treated with anti-BCMA CAR T-cell therapy. Clin. Cancer Res. 27, 6384–6392 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Huang, L. et al. Efficacy and safety of CD19 CAR-T cell therapy for patients with B cell acute lymphoblastic leukemia involving extramedullary relapse. Zhejiang Da Xue Xue Bao Yi Xue Ban 51, 151–159 (2022).

CAS  PubMed  PubMed Central  Google Scholar 

Yang, T. T. et al. Comparable outcomes in patients with B-cell acute lymphoblastic leukemia receiving haploidentical hematopoietic stem cell transplantation: Pretransplant minimal residual disease-negative complete remission following chimeric antigen receptor T-cell therapy versus chemotherapy. Front. Immunol. 13, 934442 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhou, N. & Bao, J. FerrDb: a manually curated resource for regulators and markers of ferroptosis and ferroptosis-disease associations. Database (Oxford) 2020, baaa021 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Imam, M. U., Zhang, S., Ma, J., Wang, H. & Wang, F. Antioxidants mediate both iron homeostasis and oxidative stress. Nutrients 9, 671 (2017).

Article  PubMed  PubMed Central  Google Scholar 

Hoy, A. J., Nagarajan, S. R. & Butler, L. M. Tumour fatty acid metabolism in the context of therapy resistance and obesity. Nat. Rev. Cancer 21, 753–766 (2021).

Article  CAS  PubMed  Google Scholar 

Stockwell, B. R. Ferroptosis turns 10: Emerging mechanisms, physiological functions, and therapeutic applications. Cell 185, 2401–2421 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yanatori, I., Nishina, S., Kishi, F. & Hino, K. Newly uncovered biochemical and functional aspects of ferritin. FASEB J. 37, e23095 (2023).

Article  CAS  PubMed  Google Scholar 

Scarpellini, C. et al. Beyond ferrostatin-1: a comprehensive review of ferroptosis inhibitors. Trends Pharmacol. Sci. 44, 902–916 (2023).

Article  CAS  PubMed  Google Scholar 

Wang, W. et al. CD8+ T cells regulate tumour ferroptosis during cancer immunotherapy. Nature 569, 270–274 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Giavridis, T. et al. CAR T cell-induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade. Nat. Med. 24, 731–738 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang, D. D. Ironing out the details of ferroptosis. Nat. Cell Biol. 26, 1386–1393 (2024).

Article  CAS  PubMed  Google Scholar 

Hou, W. et al. Autophagy promotes ferroptosis by degradation of ferritin. Autophagy 12, 1425–1428 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen, J. et al. Tuning charge density of chimeric antigen receptor optimizes tonic signaling and CAR-T cell fitness. Cell Res. 33, 341–354 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yu, Y. et al. Ferroptosis: a cell death connecting oxidative stress, inflammation and cardiovascular diseases. Cell Death Discov. 7, 193 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Huang, Y. et al. Rewiring mitochondrial metabolism to counteract exhaustion of CAR-T cells. J. Hematol. Oncol. 15, 38 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gao, M., Monian, P., Quadri, N., Ramasamy, R. & Jiang, X. Glutaminolysis and transferrin regulate ferroptosis. Mol. Cell 59, 298–308 (2015).

Article  CAS  PubMed 

Comments (0)

No login
gif