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Cited by 912

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 access
Liao, Peng, Wang, Weimin, Wang, Weichao, Kryczek, Ilona, Li, Xiong, Bian, Yingjie, Sell, Amanda, Wei, Shuang, Grove, Sara, Johnson, Jeffrey K., Kennedy, Paul D., Gijón, Miguel, Shah, Yatrik M., Zou, Weiping·2022·Cancer Cell

Abstract

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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Crossref · 10.1016/j.ccell.2022.02.003

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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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CoChat. (2026). Citation check: CD8+ T cells and fatty acids orchestrate tumor ferroptosis and immunity via ACSL4. https://app.cochat.ai/papers/10.1016/j.ccell.2022.02.003
The paper
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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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.