The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
CD8+ T cells and fatty acids orchestrate tumor ferroptosis and immunity via ACSL4
Open accessAbstract
SUMMARY Tumor cell intrinsic ferroptosis initiating mechanisms are unknown. Here, we discover T cell-derived interferon (IFN)γ in combination with arachidonic acid (AA) induces immunogenic tumor ferroptosis, serving as a mode of action for CD8+ T cell (CTL)-mediated tumor killing. Mechanistically, IFNγ stimulates ACSL4 and alters tumor cell lipid pattern, thereby increasing incorporations of AA into C16 and C18 acyl chain-containing phospholipids. Palmitoleic acid and oleic acid, two common C16 and C18 fatty acids in blood, promote ACSL4-dependent tumor ferroptosis induced by IFNγ plus AA. Moreover, tumor ACSL4 deficiency accelerates tumor progression. Low-dose AA enhances tumor ferroptosis and elevates spontaneous and immune checkpoint blockade (ICB)-induced anti-tumor immunity. Clinically, tumor ACSL4 correlates with T cell signatures and improved survival in ICB-treated cancer patients. Thus, IFNγ signaling paired with selective fatty acids is a natural tumor ferroptosis promoting mechanism and a mode of action of CTLs. Targeting ACSL4 pathway is a potential anti-cancer approach.
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Cited by
Tong, X., Tang, R., Xiao, M., Xu, J., Wang, W., Zhang, B., Liu, J., Yu, X., & Shi, S. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01392-3 · Cited by 883
Self-citationFerroptosis surveillance independent of GPX4 and differentially regulated by sex hormones
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Yang, F., Xiao, Y., Ding, J.-H., Jin, X., Ma, D., Li, D.-Q., Shi, J.-X., Huang, W., Wang, Y.-P., Jiang, Y.-Z., et al. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2022.09.021 · Cited by 624
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Acyl-CoA synthase ACSL4: an essential target in ferroptosis and fatty acid metabolism
Ding, K., Liu, C., Li, L., Yang, M., Jiang, N., Luo, S., & Sun, L. (2023) · Chinese Medical Journal · doi:10.1097/cm9.0000000000002533 · Cited by 396
Metadata
- Authors
- Liao, P., Wang, W., Wang, W., Kryczek, I., Li, X., Bian, Y., Sell, A., Wei, S., Grove, S., Johnson, J. K., Kennedy, P. D., Gijón, M., Shah, Y. M., & Zou, W.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2022-04
- Volume
- 40
- Issue
- 4
- Pages
- 365-378.e6
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W4213455992
- Cited by
- 912
- References
- 49
- FWCI
- 101.48
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Liao, P., Wang, W., Wang, W., Kryczek, I., Li, X., Bian, Y., Sell, A., Wei, S., Grove, S., Johnson, J. K., Kennedy, P. D., Gijón, M., Shah, Y. M., & Zou, W. (2022). CD8+ T cells and fatty acids orchestrate tumor ferroptosis and immunity via ACSL4. Cancer Cell. https://doi.org/10.1016/j.ccell.2022.02.003
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