Lactate in the tumour microenvironment: From immune modulation to therapy

EBioMedicine, Год журнала: 2021, Номер 73, С. 103627 - 103627

Опубликована: Окт. 15, 2021

Disordered metabolic states, which are characterised by hypoxia and elevated levels of metabolites, particularly lactate, contribute to the immunosuppression in tumour microenvironment (TME). Excessive lactate secreted metabolism-reprogrammed cancer cells regulates immune responses via causing extracellular acidification, acting as an energy source shuttling between different cell populations, inhibiting mechanistic (previously 'mammalian') target rapamycin (mTOR) pathway cells. This review focuses on recent advances regulation well therapeutic strategies targeting anabolism transport TME, such those involving glycolytic enzymes monocarboxylate transporter inhibitors. Considering multifaceted roles metabolism, a comprehensive understanding how lactate-targeting therapies regulate TME will provide insights into complex relationships metabolism antitumour immunity.

Язык: Английский

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Single-Cell RNA Sequencing of Tumor-Infiltrating NK Cells Reveals that Inhibition of Transcription Factor HIF-1α Unleashes NK Cell Activity

Immunity, Год журнала: 2020, Номер 52(6), С. 1075 - 1087.e8

Опубликована: Май 22, 2020

Язык: Английский

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Targeting the PI3K/AKT/mTOR Signaling Pathway in Lung Cancer: An Update Regarding Potential Drugs and Natural Products

Molecules, Год журнала: 2021, Номер 26(13), С. 4100 - 4100

Опубликована: Июль 5, 2021

Lung cancer is one of the most common cancers and has a high mortality rate. Due to its incidence, clinical management disease remains major challenge. Several reports have documented relationship between phosphatidylinositol-3-kinase (PI3K)/ protein kinase B (AKT)/ mammalian target rapamycin (mTOR) pathway lung cancer. The recognition this as notable therapeutic in mainly due central involvement initiation progression disease. Interest using natural synthetic medications these signaling pathways increased recent years, with promising results vitro, vivo, trials. In review, we focus on current understanding PI3K/AKT/mTOR tumor development. addition pathway, highlighted potential recently developed inhibitors based preclinical

Язык: Английский

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Warburg effect in colorectal cancer: the emerging roles in tumor microenvironment and therapeutic implications

Journal of Hematology & Oncology, Год журнала: 2022, Номер 15(1)

Опубликована: Ноя. 1, 2022

Colorectal cancer (CRC) is the third most common and second leading cause of cancer-related death worldwide. Countless CRC patients undergo disease progression. As a hallmark cancer, Warburg effect promotes metastasis remodels tumor microenvironment, including promoting angiogenesis, immune suppression, cancer-associated fibroblasts formation drug resistance. Targeting metabolism would be promising method for treatment CRC. In this review, we summarize information about roles in microenvironment to elucidate mechanisms governing identify novel targets therapy.

Язык: Английский

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Cellular and Extracellular Components in Tumor Microenvironment and Their Application in Early Diagnosis of Cancers

Analytical Cellular Pathology, Год журнала: 2020, Номер 2020, С. 1 - 13

Опубликована: Янв. 8, 2020

Tumors are surrounded by complex environmental components, including blood and lymph vessels, fibroblasts, endothelial cells, immune cytokines, extracellular vesicles, matrix. All the stromal components together with tumor cells form microenvironment (TME). In addition, physical chemical factors, pH, hypoxia, elevated interstitial fluid pressure, fibrosis, closely associated progression, metastasis, immunosuppression, drug resistance. Cellular in TME contribute to nearly all procedures of carcinogenesis. By summarizing recent work this field, we make a comprehensive review on role cellular process carcinogenesis their potential application early diagnosis cancer. We hope that systematic diverse aspects will help both research scientists clinicians field.

Язык: Английский

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Tumor microenvironment in glioblastoma: Current and emerging concepts

Neuro-Oncology Advances, Год журнала: 2023, Номер 5(1)

Опубликована: Янв. 1, 2023

Glioblastoma (GBM) tumor microenvironment (TME) is a highly heterogeneous and complex system, which in addition to cancer cells, consists of various resident brain immune cells as well transit through the such marrow-derived cells. The TME dynamic environment heavily influenced by alterations cellular composition, cell-to-cell contact metabolic products other chemical factors, pH oxygen levels. Emerging evidence suggests that GBM appear reprogram their TME, hijack microenvironmental elements facilitate rapid proliferation, invasion, migration, survival thus generating treatment resistance. interact with directly interaction mediated cell-surface molecules, or indirectly apocrine paracrine signaling via cytokines, growth extracellular vehicles. recent discovery neuron-glioma interfaces neurotransmitter-based interactions has uncovered novel mechanisms favor cell growth. Here, we review known emerging related communication between components its discuss models for studying outline current studies targeting therapeutic purposes.

Язык: Английский

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Matrix Stiffness Contributes to Cancer Progression by Regulating Transcription Factors

Cancers, Год журнала: 2022, Номер 14(4), С. 1049 - 1049

Опубликована: Фев. 18, 2022

Matrix stiffness is critical for the progression of various types cancers. In solid cancers such as mammary and pancreatic cancers, tumors often contain abnormally stiff tissues, mainly caused by extracellular matrices due to accumulation, contraction, crosslinking. Stiff trigger mechanotransduction, conversion mechanical cues matrix biochemical signaling in cells, a result determine cellular phenotypes cancer stromal cells tumors. Transcription factors are key molecules these processes, they respond crucial behaviors. The Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) one most studied transcription that regulated stiffness. YAP/TAZ activated promotes malignant including cancer-associated fibroblasts. addition, other β-catenin nuclear factor kappa B (NF-κB) also play roles mechanotransduction tissues. this review, mechanisms stiffening tissues introduced, their shown.

Язык: Английский

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Hypoxic pancreatic cancer derived exosomal miR-30b-5p promotes tumor angiogenesis by inhibiting GJA1 expression

International Journal of Biological Sciences, Год журнала: 2022, Номер 18(3), С. 1220 - 1237

Опубликована: Янв. 1, 2022

Purpose: Most patients with pancreatic ductal adenocarcinoma (PDAC) have vascular invasion and metastasis, leading to low surgical resection rate dismal prognosis. Tumor angiogenesis is related metastasis. However, anti-angiogenesis therapeutic effects in PDAC are limited. Therefore, it imperative explore molecular mechanism of PDAC. Experimental Design: scRNA-seq data were utilized delineatetranscriptional profiles endothelial cells The vitro vivo models used the role derived exosomes under hypoxic condition tumor angiogenesis. Results: Endothelial had distinct gene expression compared normal pancreas. marker genes enriched for hypoxia MiR-30b-5p significantly exosomes, which could be transferred HUVEC, resulting upregulation miR-30b-5p. Hypoxic promote tube formation migration via miR-30b-5p mediated downregulation gap junction protein GJA1. Moreover, increased new microvascular density vivo. Patients higher levels total exosomal peripheral blood plasma than healthy subjects. In addition, there significant correlations or between portal vein plasma. Conclusions: promoted by inhibiting GJA1, was a potential diagnostic

Язык: Английский

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Redox signaling at the crossroads of human health and disease

MedComm, Год журнала: 2022, Номер 3(2)

Опубликована: Март 31, 2022

Abstract Redox biology is at the core of life sciences, accompanied by close correlation redox processes with biological activities. homeostasis a prerequisite for human health, in which physiological levels nonradical reactive oxygen species (ROS) function as primary second messengers to modulate signaling orchestrating multiple sensors. However, excessive ROS accumulation, termed oxidative stress (OS), leads biomolecule damage and subsequent occurrence various diseases such type 2 diabetes, atherosclerosis, cancer. Herein, starting evolution biology, we reveal roles multifaceted modulators mediate sustain homeostasis. In addition, also emphasize detailed OS mechanisms involved initiation development several important diseases. double‐edged sword disease progression suggest two different therapeutic strategies treat redox‐relevant diseases, targeting sources redox‐related effectors manipulate will largely promote precision medicine. Therefore, comprehensive understanding networks under pathological conditions facilitate medicine benefit patients

Язык: Английский

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Functions of the aryl hydrocarbon receptor (AHR) beyond the canonical AHR/ARNT signaling pathway

Biochemical Pharmacology, Год журнала: 2022, Номер 208, С. 115371 - 115371

Опубликована: Дек. 15, 2022

Язык: Английский

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