2022
DOI: 10.1038/s41419-022-05384-6
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Ferroptosis: a double-edged sword mediating immune tolerance of cancer

Abstract: The term ferroptosis was put forward in 2012 and has been researched exponentially over the past few years. Ferroptosis is an unconventional pattern of iron-dependent programmed cell death, which belongs to a type of necrosis and is distinguished from apoptosis and autophagy. Actuated by iron-dependent phospholipid peroxidation, ferroptosis is modulated by various cellular metabolic and signaling pathways, including amino acid, lipid, iron, and mitochondrial metabolism. Notably, ferroptosis is associated with … Show more

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Cited by 57 publications
(27 citation statements)
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“…We obtained associations with pathways linking metabolism and innate immune system, such as Glutathione conjugation (R-HSA-156590) and TNFR1-induced NF-kappa-B signalling pathway (R-HSA-5357956). Therefore, the ENQUIRE-generated output highlights a potential molecular axis between metabolism, ferroptotic cell death and immune response (51, 52).…”
Section: Resultsmentioning
confidence: 99%
“…We obtained associations with pathways linking metabolism and innate immune system, such as Glutathione conjugation (R-HSA-156590) and TNFR1-induced NF-kappa-B signalling pathway (R-HSA-5357956). Therefore, the ENQUIRE-generated output highlights a potential molecular axis between metabolism, ferroptotic cell death and immune response (51, 52).…”
Section: Resultsmentioning
confidence: 99%
“…Therapeutic cancer vaccines, including sipuleucel-T, PROSTVAC, and personalized peptide vaccines, have not led to significant survival differences in patient populations [ 34 , 35 , 36 ]. Newer trials combining vaccines and other agents, the immune response, and ICIs may be able to downgrade the tumor defenses against T cells [ 37 , 38 , 39 , 40 ]. Sipuleucel-T did, however, lead to differences in T cells that were thrice activated in vaccinated patients as compared to placebo groups; therefore, the vaccine may prime patients’ immune response [ 41 , 42 , 43 , 44 ].…”
Section: Discussionmentioning
confidence: 99%
“…Indeed, we now know that ferroptosis can be suppressed by both GPX4dependent and -independent mechanisms. Once one mechanism is inactivated or exhausted, cancer cells become dependent on the other mechanism to escape ferroptosis, while becoming highly sensitive to ferroptosis-inducing conditions sensed by the original defense mechanism [382,383]. Whether a GPX4-related FASN on/off switch is similarly involved in the imbalance of the ferroptosis defense system depending on specific oncogenic mutations or specific cellular states requires further clarification.…”
Section: Fasnis and Ferroptosismentioning
confidence: 99%
“…Whether a GPX4-related FASN on/off switch is similarly involved in the imbalance of the ferroptosis defense system depending on specific oncogenic mutations or specific cellular states requires further clarification. Since immunotherapyactivated T-cells enhance ferroptosis-specific lipid peroxidation in tumor cells via IFNc-impaired uptake of the GPX4 promoter cystine [382,384,385], the involvement of FASN in prohibiting ferroptosis may also be explored for the development of pro-ferroptotic therapy in the treatment of immune-resistant, metastasisprone tumor cells. In addition, future studies should evaluate how FASTIS is associated with changes in the ferroptosis susceptibility of metastatic cancer cells, as senescent cells often accumulate and store intracellular iron as ferritin while limiting its autophagic degradation or ferritinophagy; however, excessive ferritinophagy can result in the release of large amounts of free iron, leading to lipid peroxidation and ferroptosis.…”
Section: Fasnis and Ferroptosismentioning
confidence: 99%