Metabolites and the tumour microenvironment: from cellular mechanisms to systemic metabolism

Nature Metabolism, Год журнала: 2021, Номер 3(1), С. 21 - 32

Опубликована: Янв. 4, 2021

Язык: Английский

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Amino Assets: How Amino Acids Support Immunity

Cell Metabolism, Год журнала: 2020, Номер 32(2), С. 154 - 175

Опубликована: Июль 9, 2020

Язык: Английский

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Redox regulation of immunometabolism

Nature reviews. Immunology, Год журнала: 2020, Номер 21(6), С. 363 - 381

Опубликована: Дек. 18, 2020

Язык: Английский

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Limited Environmental Serine and Glycine Confer Brain Metastasis Sensitivity to PHGDH Inhibition

Cancer Discovery, Год журнала: 2020, Номер 10(9), С. 1352 - 1373

Опубликована: Июнь 22, 2020

A hallmark of metastasis is the adaptation tumor cells to new environments. Metabolic constraints imposed by serine and glycine-limited brain environment restrict metastatic growth. How metastases overcome these growth-prohibitive conditions poorly understood. Here, we demonstrate that 3-phosphoglycerate dehydrogenase (PHGDH), which catalyzes rate-limiting step glucose-derived synthesis, a major determinant in multiple human cancer types preclinical models. Enhanced synthesis proved important for nucleotide production cell proliferation highly aggressive cells. In vivo, genetic suppression pharmacologic inhibition PHGDH attenuated metastasis, but not extracranial growth, improved overall survival mice. These results reveal extracellular amino acid availability determines pathway dependence, suggest inhibitors may be useful treatment metastasis. SIGNIFICANCE: Using proteomics, metabolomics, models, nutrient-limited potentiates susceptibility inhibition. findings underscore importance studying metabolism physiologically relevant contexts, provide rationale using treat metastasis.This article highlighted This Issue feature, p. 1241.

Язык: Английский

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Metabolic adaptation of lymphocytes in immunity and disease

Immunity, Год журнала: 2022, Номер 55(1), С. 14 - 30

Опубликована: Янв. 1, 2022

Adaptive immune responses mediated by T cells and B are crucial for protective immunity against pathogens tumors. Differentiation function of require dynamic reprogramming cellular metabolism. Metabolic inputs, pathways, enzymes display remarkable flexibility heterogeneity, especially in vivo. How metabolic plasticity adaptation dictate functional specialization is fundamental to our understanding therapeutic modulation the system. Extensive progress has been made characterizing effects networks on cell fate discrete microenvironments or immunological contexts. In this review, we summarize how rewiring metabolism determines outcome adaptive vivo, with a focus metabolites, nutrients, driver genes immunometabolism instruct programming during infection, inflammation, cancer mice humans. Understanding context-dependent remodeling will manifest legitimate opportunities intervention human disease.

Язык: Английский

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Mitochondrial oxidative stress in the tumor microenvironment and cancer immunoescape: foe or friend?

Journal of Biomedical Science, Год журнала: 2022, Номер 29(1)

Опубликована: Сен. 26, 2022

The major concept of "oxidative stress" is an excess elevated level reactive oxygen species (ROS) which are generated from vigorous metabolism and consumption oxygen. precise harmonization oxidative stresses between mitochondria other organelles in the cell absolutely vital to survival. Under stress, ROS produced mediator for tumorigenesis different aspects, such as proliferation, migration/invasion, angiogenesis, inflammation, immunoescape allow cancer cells adapt rigorous environment. Accordingly, dynamic balance not only orchestrate complex signaling events but also affect components tumor microenvironment (TME). Immune cells, M2 macrophages, dendritic T immunosuppressive TME ROS-induced inflammation. Based on this notion, numerous strategies mitigate tumors have been tested prevention or therapies; however, these manipulations devised sources mechanisms without established effectiveness. Herein, we integrate current progress regarding impact mitochondrial TME, immune discuss combination emerging ROS-modulating with immunotherapies achieve antitumor effects.

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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Amino acid metabolism in immune cells: essential regulators of the effector functions, and promising opportunities to enhance cancer immunotherapy

Journal of Hematology & Oncology, Год журнала: 2023, Номер 16(1)

Опубликована: Июнь 5, 2023

Abstract Amino acids are basic nutrients for immune cells during organ development, tissue homeostasis, and the response. Regarding metabolic reprogramming in tumor microenvironment, dysregulation of amino acid consumption is an important underlying mechanism leading to impaired anti-tumor immunity. Emerging studies have revealed that altered metabolism tightly linked outgrowth, metastasis, therapeutic resistance through governing fate various cells. During these processes, concentration free acids, their membrane bound transporters, key enzymes, sensors such as mTOR GCN2 play critical roles controlling cell differentiation function. As such, anti-cancer responses could be enhanced by supplement specific essential or targeting enzymes sensors, thereby developing novel adjuvant modalities. To further dissect regulation immunity, this review summarizes regulatory mechanisms effects on phenotypes functions tumor-infiltrating propose approaches exploited rewire enhance cancer immunotherapy.

Язык: Английский

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The Functional Crosstalk between Myeloid-Derived Suppressor Cells and Regulatory T Cells within the Immunosuppressive Tumor Microenvironment

Cancers, Год журнала: 2021, Номер 13(2), С. 210 - 210

Опубликована: Янв. 8, 2021

Immune checkpoint inhibitors (ICI) have led to profound and durable tumor regression in some patients with metastatic cancer diseases. However, many still do not derive benefit from immunotherapy. Here, the accumulation of immunosuppressive cell populations within microenvironment (TME), such as myeloid-derived suppressor cells (MDSC), tumor-associated macrophages (TAM), regulatory T (Treg), contributes development immune resistance. MDSC Treg expand systematically inhibit activation effector function. Numerous studies shown that mechanisms exerted by those inhibitory comprise soluble immunomodulatory mediators receptor interactions. The latter are also required for crosstalk Treg, raising questions about relevance cell-cell contacts establishment their properties. This review aims outline current knowledge on between these two populations, issuing particularly potential role adhesion molecules. In this regard, we further discuss β2 integrins, which essential differentiation function leukocytes well MDSC-Treg interaction. Lastly, aim describe impact bidirectional basic applied research how targeting pathways might pave way future approaches

Язык: Английский

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A guide to interrogating immunometabolism

Nature reviews. Immunology, Год журнала: 2021, Номер 21(10), С. 637 - 652

Опубликована: Апрель 15, 2021

Язык: Английский

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