CD8+ T cells and fatty acids orchestrate tumor ferroptosis and immunity via ACSL4
dc.contributor.author | Liao, P | |
dc.contributor.author | Wang, W | |
dc.contributor.author | Wang, W | |
dc.contributor.author | Kryczek, I | |
dc.contributor.author | Li, X | |
dc.contributor.author | Bian, Y | |
dc.contributor.author | Sell, A | |
dc.contributor.author | Wei, S | |
dc.contributor.author | Grove, S | |
dc.contributor.author | Johnson, J | |
dc.contributor.author | Kennedy, P | |
dc.contributor.author | Gijón, M | |
dc.contributor.author | Shah, Y | |
dc.contributor.author | Zou, W | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2023-12-05T20:06:15Z | |
dc.date.available | 2023-12-05T20:06:15Z | |
dc.date.issued | 2021-01-01 | |
dc.identifier.issn | 1535-6108 | |
dc.identifier.issn | 1878-3686 | |
dc.identifier.uri | https://www.ncbi.nlm.nih.gov/pubmed/35216678 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/191682 | en |
dc.description.abstract | Tumor cell intrinsic ferroptosis-initiating mechanisms are unknown. Here, we discover that 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 the ACSL4 pathway is a potential anti-cancer approach. | |
dc.format.medium | Print-Electronic | |
dc.language | eng | |
dc.publisher | Elsevier | |
dc.subject | ACSL4 | |
dc.subject | PD-L1 | |
dc.subject | T cell | |
dc.subject | arachidonic acid | |
dc.subject | cancer | |
dc.subject | ferroptosis | |
dc.subject | immunotherapy | |
dc.subject | interferon | |
dc.subject | oleic acid | |
dc.subject | palmitoleic acid | |
dc.subject | CD8-Positive T-Lymphocytes | |
dc.subject | Coenzyme A Ligases | |
dc.subject | Fatty Acids | |
dc.subject | Ferroptosis | |
dc.subject | Humans | |
dc.subject | Neoplasms | |
dc.title | CD8+ T cells and fatty acids orchestrate tumor ferroptosis and immunity via ACSL4 | |
dc.type | Article | |
dc.identifier.pmid | 35216678 | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/191682/2/CD8sup+sup T cells and fatty acids orchestrate tumor ferroptosis and immunity via ACSL4.pdf | |
dc.identifier.doi | 10.1016/j.ccell.2022.02.003 | |
dc.identifier.doi | https://dx.doi.org/10.7302/21862 | |
dc.identifier.source | Cancer Cell | |
dc.description.version | Published version | |
dc.date.updated | 2023-12-05T20:06:05Z | |
dc.identifier.orcid | 0000-0002-8409-5574 | |
dc.identifier.orcid | 0000-0002-3130-2533 | |
dc.identifier.orcid | 0000-0002-2703-5268 | |
dc.identifier.orcid | 0000-0002-2487-4816 | |
dc.identifier.orcid | 0000-0001-7952-3549 | |
dc.description.filedescription | Description of CD8sup+sup T cells and fatty acids orchestrate tumor ferroptosis and immunity via ACSL4.pdf : Published version | |
dc.identifier.volume | 40 | |
dc.identifier.issue | 4 | |
dc.identifier.startpage | 365 | |
dc.identifier.endpage | 378.e6 | |
dc.identifier.name-orcid | Liao, P; 0000-0002-8409-5574 | |
dc.identifier.name-orcid | Wang, W | |
dc.identifier.name-orcid | Wang, W | |
dc.identifier.name-orcid | Kryczek, I; 0000-0002-3130-2533 | |
dc.identifier.name-orcid | Li, X | |
dc.identifier.name-orcid | Bian, Y | |
dc.identifier.name-orcid | Sell, A | |
dc.identifier.name-orcid | Wei, S; 0000-0002-2703-5268 | |
dc.identifier.name-orcid | Grove, S | |
dc.identifier.name-orcid | Johnson, J | |
dc.identifier.name-orcid | Kennedy, P | |
dc.identifier.name-orcid | Gijón, M | |
dc.identifier.name-orcid | Shah, Y; 0000-0002-2487-4816 | |
dc.identifier.name-orcid | Zou, W; 0000-0001-7952-3549 | |
dc.working.doi | 10.7302/21862 | en |
dc.owningcollname | Surgery, Department of |
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