PPARG-mediated ferroptosis in dendritic cells limits antitumor immunity

Han, Leng; Bai, Lulu; Qu, Chunjing; Dai, Enyong; Liu, Jiao; Kang, Rui; Zhou, Di; Tang, Daolin

doi:10.1016/j.bbrc.2021.08.082

Cited by 55 publications

(41 citation statements)

References 29 publications

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“…The first is that induction of ferroptosis in cancer cells by itself changed little, if any, systemic or local immunity in the TME. This seemed to be contradictory to the previous observations made by others [ 33 , 34 ]. However, our observation is from the net immunological effect in the TME.…”

Section: Discussioncontrasting

confidence: 99%

“…Few, if any, studies address whether tumor cells undergoing ferroptosis can enhance antitumor immunity in vivo. As for the function of ferroptosis in immune cells, two studies show that ferroptosis can dampen DC and CD8 + T cell functions [ 33 , 34 ]. Interestingly, Wang et al reported that CD8 + T cells induced ferroptosis in cancer cells in vivo [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, CD36-mediated ferroptosis dampens intratumoral CD8 + T cell effector function and impairs its antitumor ability [ 33 ]. In addition, PPARG-mediated ferroptosis in dendritic cells limits antitumor immunity [ 34 ]. On tumor cells, as ferroptosis is a form of ICD and can release various DAMPs, it is thought to be immunogenic when cancer cells are induced to undergo ferroptosis.…”

Section: Introductionmentioning

confidence: 99%

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Ferroptosis Inducer Improves the Efficacy of Oncolytic Virus-Mediated Cancer Immunotherapy

Chen

Zhu

et al. 2022

Biomedicines

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Ferroptosis is a type of programmed cell death dependent on iron and characterized by the accumulation of lipid peroxides. In this study, we explore the combination of a ferroptosis activator with an oncolytic vaccinia virus in tumor models. Erastin induced cell death in hepatoma, colon, and ovarian cancer cells, but not in melanoma cancer cells. Erastin, not the oncolytic vaccinia virus (OVV), induced the expression of key marker genes for ferroptosis in cancer cells. In hepatocellular carcinoma and colon cancer models, either erastin or OVV inhibited tumor growth, but a combination of the two yielded the best therapeutic effects, as indicated by inhibited tumor growth or regression and longer host survival. Immunological analyses indicate that erastin alone had little or no effect on systemic immunity or local immunity in the tumor. However, when combined with OV, erastin enhanced the number of activated dendritic cells and the activity of tumor-infiltrating T lymphocytes as indicated by an increase in IFN-γ+CD8+ and PD-1+CD8+ T cells. These results demonstrate that erastin can exert cytotoxicity on cancer cells via ferroptosis, but has little effect on immune activity by itself. However, when combined with an OVV, erastin promoted antitumoral immunity and efficacy by increasing the number of activated dendritic cells and promoting the activities of tumor specific CD8+ T cells in the tumor.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ferroptosis Inducer Improves the Efficacy of Oncolytic Virus-Mediated Cancer Immunotherapy

Chen

Zhu

et al. 2022

Biomedicines

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“…Studies have found that RSL3 (GXP4 inhibitor) can be responsible for inducing ferroptosis through PPARG, which blocks DCs maturation, weakens the ability of DCs to secrete TNF and IL6, and reduces MHC class I expression in response to lipopolysaccharide signals. In addition, after ferroptosis happens to DCs, they cannot induce CD8 + T cells to produce IFNγ ( 80 ). It is well known that the antigen presentation ability and anti-tumor ability of DCs decrease in TME, it may result from the occurrence of ferroptosis induced by lipid accumulation in DCs ( 81 ).…”

Section: Immune Cells and Ferroptosismentioning

confidence: 99%

Ferroptosis: A Critical Moderator in the Life Cycle of Immune Cells

Wang

2022

Front. Immunol.

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Ferroptosis is a form of programmed cell death that was only recognized in 2012. Until recently, numerous researchers have turned their attention to the mechanism and function of ferroptosis. A large number of studies have shown potential links between cell ferroptosis and infection, inflammation, and tumor. At the same time, immune cells are vital players in these above-mentioned processes. To date, there is no comprehensive literature review to summarize the relationship between ferroptosis and immune cells. Therefore, it is of great significance to explore the functional relationship between the two. This review will attempt to explain the link between ferroptosis and various immune cells, as well as determine the role ferroptosis plays in infection, inflammation, and malignancies. From this, we may find the potential therapeutic targets of these diseases.

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“…Several studies in other cancers have shown that DAMP released during erastininduced ferroptosis may activate adaptive tumor immunity to inhibit tumor growth (Efimova et al, 2020;Tang et al, 2020b). However, the occurrence of ferroptosis in dendritic cells or CD8 + T cells can impair their anti-tumor function (Han et al, 2021;Ma et al, 2021). In the next few years, the impact of genetic mutations, degradation pathways, and metabolic plasticity on susceptibility to ferroptosis in the different component cells of the tumor microenvironment will be an active area of research (Chen et al, 2021e;Chen et al, 2021f;Tang et al, 2021).…”

Section: Opportunities and Challengesmentioning

confidence: 99%

The Art of War: Ferroptosis and Pancreatic Cancer

2021

Self Cite

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Pancreatic cancer is a devastating gastrointestinal cancer, characterized by late diagnosis, low treatment success rate, and poor survival prognosis. The most common pathological type of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC), which is mainly driven by the K-Ras oncogene. Ferroptosis was originally described as Ras-dependent cell death, but is now defined as lipid peroxidation-mediated regulated necrosis, accompanied by excessive activation of the autophagy degradation pathway and limited membrane repair capacity. The impaired ferroptotic pathway is involved in many types of cancer, including PDAC. On the one hand, the chronic inflammation caused by ferroptotic damage contributes to the formation of K-Ras-driven PDAC. On the other hand, drug-induced ferroptosis is an emerging strategy to suppress tumor growth in established PDAC. In this mini-review, we outline the core process of ferroptosis, discuss the regulatory mechanism of ferroptosis in PDAC, and highlight some of the challenges of targeting ferroptosis in PDAC therapy.

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PPARG-mediated ferroptosis in dendritic cells limits antitumor immunity

Cited by 55 publications

References 29 publications

Ferroptosis Inducer Improves the Efficacy of Oncolytic Virus-Mediated Cancer Immunotherapy

Ferroptosis Inducer Improves the Efficacy of Oncolytic Virus-Mediated Cancer Immunotherapy

Ferroptosis: A Critical Moderator in the Life Cycle of Immune Cells

The Art of War: Ferroptosis and Pancreatic Cancer

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