Tumor aerobic glycolysis confers immune evasion through modulating sensitivity to T cell-mediated bystander killing via TNF-α

Wu, Ling; Jin, Yiteng; Zhao, Xiaoyu; Tang, Kun; Zhao, Yidan; Tong, Liang; Yu, Xuerong; Xiong, Ke; Luo, Ce; Zhu, Jiajun; Wang, Xinghuan; Zeng, Zexian; Pan, Deng

doi:10.1016/j.cmet.2023.07.001

Cited by 72 publications

(30 citation statements)

References 78 publications

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“…297 Cu BiSex nanozymes with POD-like activity can aggregate and interact with mitochondrial acylated proteins, leading to cuproptosis in tumor cells. (6) In contrast to natural enzymes, the release of transition metals in vivo may lead to potential metal ion toxicity, thereby impeding clinical translation. Hence, it is imperative to conduct comprehensive and systematic biosafety assessments that encompass biocompatibility and biodegradability aspects, which will facilitate the clinical translation of nanozymes.…”

Section: Discussionmentioning

confidence: 99%

“…3−5 Furthermore, the lack of glucose and O 2 leads to glycolysis blockage, reducing antioxidant capacity related to glycolysis and accelerating reactive oxygen species (ROS) generation including singlet oxygen ( 1 O 2 ), superoxide anions (O 2 −• ), hydroxyl radicals ( • OH), hydrogen peroxide (H 2 O 2 ), etc. 6,7 Tumor cells adapt to high ROS concentrations through a robust redox system, resulting in TME exhibiting higher ROS/ GSH levels than normal cells. 8,9 This special TME greatly compromises the therapeutic effect of traditional treatment methods such as radiotherapy (RT) and chemotherapy, forcing the use of high-dose drugs with serious side effects.…”

Section: Introductionmentioning

confidence: 99%

“…Cancer is a malignant disease characterized by uncontrolled proliferation of tumor cells, resulting in millions of deaths worldwide annually. , The excessive growth of tumor cells creates a complex tumor microenvironment (TME), which typically exhibits hypoxia and acidic conditions due to the rapid metabolism of glucose and oxygen (O 2 ) consumption, leading to overproduction of metabolites such as lactate. − Furthermore, the lack of glucose and O 2 leads to glycolysis blockage, reducing antioxidant capacity related to glycolysis and accelerating reactive oxygen species (ROS) generation including singlet oxygen ( 1 O 2 ), superoxide anions (O 2 –• ), hydroxyl radicals ( • OH), hydrogen peroxide (H 2 O 2 ), etc. , Tumor cells adapt to high ROS concentrations through a robust redox system, resulting in TME exhibiting higher ROS/GSH levels than normal cells. , This special TME greatly compromises the therapeutic effect of traditional treatment methods such as radiotherapy (RT) and chemotherapy, forcing the use of high-dose drugs with serious side effects. − Moreover, cancer mortality rates remain high while recurrence rates expose weaknesses in current treatments for containing cancer progression; , therefore, it is imperative that other cancer treatment strategies be developed for improving antitumor efficiency.…”

Section: Introductionmentioning

confidence: 99%

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Transition-Metal-Based Nanozymes: Synthesis, Mechanisms of Therapeutic Action, and Applications in Cancer Treatment

Fu,

Wei,

Wang

2024

ACS Nano

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Cancer, as one of the leading causes of death worldwide, drives the advancement of cutting-edge technologies for cancer treatment. Transition-metal-based nanozymes emerge as promising therapeutic nanodrugs that provide a reference for cancer therapy. In this review, we present recent breakthrough nanozymes for cancer treatment. First, we comprehensively outline the preparation strategies involved in creating transition-metal-based nanozymes, including hydrothermal method, solvothermal method, chemical reduction method, biomimetic mineralization method, and sol−gel method. Subsequently, we elucidate the catalytic mechanisms (catalase (CAT)-like activities), peroxidase (POD)-like activities), oxidase (OXD)-like activities) and superoxide dismutase (SOD)-like activities) of transition-metal-based nanozymes along with their activity regulation strategies such as morphology control, size manipulation, modulation, composition adjustment and surface modification under environmental stimulation. Furthermore, we elaborate on the diverse applications of transition-metal-based nanozymes in anticancer therapies encompassing radiotherapy (RT), chemodynamic therapy (CDT), photodynamic therapy (PDT), photothermal therapy (PTT), sonodynamic therapy (SDT), immunotherapy, and synergistic therapy. Finally, the challenges faced by transition-metal-based nanozymes are discussed alongside future research directions. The purpose of this review is to offer scientific guidance that will enhance the clinical applications of nanozymes based on transition metals.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Transition-Metal-Based Nanozymes: Synthesis, Mechanisms of Therapeutic Action, and Applications in Cancer Treatment

Fu,

Wei,

Wang

2024

ACS Nano

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“…Our multipronged analysis highlighted role of multiple genes in EGFR-TAD in aerobic glycolysis and related functions, which reveal a link between an evolutionary force associated with development larger brain and severity in cancer. In addition to cell-cycle and drug-resistance, aerobic glycolysis has also also been associated with immune evasion of tumor cells by modulation of T cell activity [41]. Hence targeting glycolysis or related genes in EGFR-TAD can possibly help in improving effectiveness of cancer immunotherapy [41] [42].…”

Section: Discussionmentioning

confidence: 99%

Deciphering drug response and phenotypic heterogeneity of cancer cells using gene ensembles of regulatory units defined by chromatin domains

Pandey

Sharma

Mathur

et al. 2023

Preprint

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Chromatin is organised in the form of domains known to be insulated from neighbouring regions in the genome. The colocalisation of genes sharing similar functions in the topologically associated domains (TAD) and the orchestration of their activity in cancer-cells and their drug-response have not been comprehensively explored. Here we analyzed patterns in the activity of TADs in cancer-cells along with chromatin interaction profiles to understand their modes of drug-response. Using our approach on the transcriptome of 819 cancer cell lines revealed that for multiple drugs, IC50 values were substantially more correlated with the activity of a few TADs than any of the genes. Such a result signifies the potential utility of TAD activity in highlighting common mechanisms of drug response in spite of heterogeneity in the association of genes with drug-resistance. Further we performed analysis of 9014 cancer sample transcriptomes from 20 cancer types to find the relationship between TAD-activity and survival to highlight context of cause and actionable mechanism for better therapy. Overall our analysis highlighted higher importance and influence of combinatorics of genes in many TADs in comparison to independent effect of their own genes , on the patient-survival and drug-response of cancer-cells.

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“…Reprogramming of glycolysis is a hallmark of tumors. Wu et al [30] found that deletion of two important glycolytic enzymes, GLUT1 and glucose-6-phosphate isomerase 1, resulted in enhanced tumor cell killing by cytotoxic T lymphocytes (CTL). Inactivation of GLUT1 leads to metabolic rewiring toward oxidative phosphorylation, which in turn leads to excessive reactive oxygen species (ROS) production in tumor cells, sensitive to the tumor necrosis factor alpha (TNF-α)-mediated death pathway in CTLs.…”

Section: Glucosementioning

confidence: 99%

Targeting metabolism to improve CAR-T cells therapeutic efficacy

Liu,

Zhao,

Gao

et al. 2024

Chinese Medical Journal

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Chimeric antigen receptor T (CAR-T) cell therapy achieved advanced progress in the treatment of hematological tumors. However, the application of CAR-T cell therapy for solid tumors still faces many challenges. Competition with tumor cells for metabolic resources in an already nutrient-poor tumor microenvironment is a major contributing cause to CAR-T cell therapy’s low effectiveness. Abnormal metabolic processes are now acknowledged to shape the tumor microenvironment, which is characterized by increased interstitial fluid pressure, low pH level, hypoxia, accumulation of immunosuppressive metabolites, and mitochondrial dysfunction. These factors are important contributors to restriction of T cell proliferation, cytokine release, and suppression of tumor cell-killing ability. This review provides an overview of how different metabolites regulate T cell activity, analyzes the current dilemmas, and proposes key strategies to reestablish the CAR-T cell therapy’s effectiveness through targeting metabolism, with the aim of providing new strategies to surmount the obstacle in the way of solid tumor CAR-T cell treatment.

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Tumor aerobic glycolysis confers immune evasion through modulating sensitivity to T cell-mediated bystander killing via TNF-α

Cited by 72 publications

References 78 publications

Transition-Metal-Based Nanozymes: Synthesis, Mechanisms of Therapeutic Action, and Applications in Cancer Treatment

Transition-Metal-Based Nanozymes: Synthesis, Mechanisms of Therapeutic Action, and Applications in Cancer Treatment

Deciphering drug response and phenotypic heterogeneity of cancer cells using gene ensembles of regulatory units defined by chromatin domains

Targeting metabolism to improve CAR-T cells therapeutic efficacy

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