Ferroptosis in the tumor microenvironment: perspectives for immunotherapy

Trends in Molecular Medicine, Год журнала: 2021, Номер 27(9), С. 856 - 867

Опубликована: Июль 23, 2021

Язык: Английский

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Oxidative Stress in the Tumor Microenvironment and Its Relevance to Cancer Immunotherapy

Cancers, Год журнала: 2021, Номер 13(5), С. 986 - 986

Опубликована: Фев. 27, 2021

It has been well-established that cancer cells are under constant oxidative stress, as reflected by elevated basal level of reactive oxygen species (ROS), due to increased metabolism driven aberrant cell growth. Cancer can adapt maintain redox homeostasis through a variety mechanisms. The prevalent perception about ROS is they one the key drivers promoting tumor initiation, progression, metastasis, and drug resistance. Based on this notion, numerous antioxidants aim mitigate stress have tested for prevention or treatment, although effectiveness strategy yet be established. In recent years, it increasingly appreciated complex, multifaceted role in microenvironment (TME), targeted amplify inside cause destruction. Accumulating evidence indicates immunotherapies alter intensify resulting ROS-dependent rejection. Herein we review progresses regarding impact various immune TME, discuss emerging ROS-modulating strategies used combination with achieve enhanced antitumor effects.

Язык: Английский

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Molecular basis for redox control by the human cystine/glutamate antiporter system xc−

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Дек. 8, 2021

Cysteine plays an essential role in cellular redox homoeostasis as a key constituent of the tripeptide glutathione (GSH). A rate limiting step GSH synthesis is availability cysteine. However, circulating cysteine exists blood oxidised di-peptide cystine, requiring specialised transport systems for its import into cell. System xc

Язык: Английский

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The Role of Cystine/Glutamate Antiporter SLC7A11/xCT in the Pathophysiology of Cancer

Frontiers in Oncology, Год журнала: 2022, Номер 12

Опубликована: Фев. 23, 2022

SLC7A11/xCT is an antiporter that mediates the uptake of extracellular cystine in exchange for glutamate. Cystine reduced to cysteine, which a rate-limiting precursor glutathione synthesis; process protects cells from oxidative stress and is, therefore, critical cell growth, proliferation, metabolism. SLC7A11 expressed different tissues plays diverse functional roles pathophysiology various diseases, including cancer, by regulating processes redox homeostasis, metabolic flexibility/nutrient dependency, immune system function, ferroptosis. expression associated with poor prognosis drug resistance cancer and, represents important therapeutic target. In this review, we discuss molecular functions normal

Язык: Английский

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Targeting SLC3A2 subunit of system XC− is essential for m6A reader YTHDC2 to be an endogenous ferroptosis inducer in lung adenocarcinoma

Free Radical Biology and Medicine, Год журнала: 2021, Номер 168, С. 25 - 43

Опубликована: Март 27, 2021

Язык: Английский

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STAT6 inhibits ferroptosis and alleviates acute lung injury via regulating P53/SLC7A11 pathway

Cell Death and Disease, Год журнала: 2022, Номер 13(6)

Опубликована: Июнь 6, 2022

Abstract Compelling evidences have revealed the emerging role of ferroptosis in pathophysiological process acute lung injury (ALI), but its modulation is not clear. Here, we identified that STAT6 acted as a critical regulator epithelium during ALI. Firstly, expression and activity were increased ALI mice models caused by crystalline silica (CS), LPS X-ray exposure. Followed confirming contribution above with ferrostatin-1 deferoxamine intervention, bioinformatic analyses was negatively correlated ferroptosis. Consistently, epithelium-specific depletion or knockdown cultured epithelial cells exacerbated While overexpression attenuated Mechanistically, SLC7A11 typical ferroptosis-related gene regulated P53. CREB-binding protein (CBP) acetyltransferase P53 acetylation, showing valuable regulation on targets’ transcription. Herein, found regulates through competitively binding CBP, which inhibits acetylation transcriptionally restores expression. Finally, pulmonary-specific decreased CS induced injury. Our findings pivotal ferroptosis, may be potential therapeutic target for treatment

Язык: Английский

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Targeted xCT‐mediated Ferroptosis and Protumoral Polarization of Macrophages Is Effective against HCC and Enhances the Efficacy of the Anti‐PD‐1/L1 Response

Advanced Science, Год журнала: 2022, Номер 10(2)

Опубликована: Ноя. 28, 2022

Abstract Tumor‐associated macrophages (TAMs) play an essential role in tumor progression, metastasis, and antitumor immunity. Ferroptosis has attracted extensive attention for its lethal effect on cells, but the of ferroptosis TAMs impact progression have not been clearly defined. Using transgenic mouse models, this study determines that xCT‐specific knockout is sufficient to limit tumorigenicity metastasis HCC achieved by reducing TAM recruitment infiltration, inhibiting M2‐type polarization, activating enhancing activity within TAMs. The SOCS3‐STAT6‐PPAR‐ γ signaling may be a crucial pathway macrophage phenotypic shifting, activation intracellular associated with GPX4/RRM2 regulation. Furthermore, xCT‐mediated significantly increases PD‐L1 expression improves efficacy anti‐PD‐L1 therapy unveiled. constructed Man@pSiNPs‐erastin specifically targets protumoral polarization combining treatment exerts substantial efficacy. xCT tissues, especially CD68+ macrophages, can serve as reliable factor predict prognosis patients. These findings provide further insight into targeting regulating infiltration functional achieve precise prevention improve therapeutic

Язык: Английский

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Disulfidptosis: disulfide stress–induced cell death

Trends in Cell Biology, Год журнала: 2023, Номер 34(4), С. 327 - 337

Опубликована: Авг. 12, 2023

Язык: Английский

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Transsulfuration, minor player or crucial for cysteine homeostasis in cancer

Trends in Cell Biology, Год журнала: 2022, Номер 32(9), С. 800 - 814

Опубликована: Март 29, 2022

Cysteine, a thiol-containing amino acid, is crucial for the synthesis of sulfur-containing biomolecules that control multiple essential cellular activities. Altered cysteine metabolism has been linked to numerous driver oncoproteins and tumor suppressors, as well malignant traits in cancer. Cysteine can be acquired from extracellular sources or synthesized de novo via transsulfuration (TSS) pathway. Limited availability cystine interstitial fluids raises possible dependency on TSS. However, contribution TSS cancer remains highly contentious. Based recent findings, we provide new perspectives this but understudied metabolic pathway

Язык: Английский

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SLC7A11 as a Gateway of Metabolic Perturbation and Ferroptosis Vulnerability in Cancer

Antioxidants, Год журнала: 2022, Номер 11(12), С. 2444 - 2444

Опубликована: Дек. 11, 2022

SLC7A11 is a cell transmembrane protein composing the light chain of system xc-, transporting extracellular cystine into cells for cysteine production and GSH biosynthesis. critical gateway redox homeostasis by maintaining cellular levels that counter oxidative stress suppress ferroptosis. overexpressed in various human cancers regulates tumor development, proliferation, metastasis, microenvironment, treatment resistance. Upregulation needed to adapt high microenvironments maintain homeostasis. High basal ROS dependences cancer render them vulnerable further stress. Therefore, cyst(e)ine depletion may be an effective new strategy treatment. However, effectiveness inhibitors or cyst(e)inase has been established many preclinical studies but not reached stage clinical trials patients. A better understanding functions regulating interacting with redox-active proteins their substrates could promising this review intends understand role antioxidant signaling, regulators bioavailability cancer, linking signaling metabolism targeting novel therapeutics.

Язык: Английский

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