Yes associated protein 1 promotes resistance to 5-fluorouracil in gastric cancer by regulating GLUT3-dependent glycometabolism reprogramming of tumor-associated macrophages

He, Zhanke; Chen, Da; Wu, Jiani; Sui, Chuyang; Deng, Xiangqian; Zhang, Penghao; Chen, Zechang; Liu, Diankun; Yu, Jiang; Shi, Jiaolong; Li, Guoxin; Yao, Xiang

doi:10.1016/j.abb.2021.108838

Cited by 32 publications

(28 citation statements)

References 37 publications

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“…Increasing evidence has revealed the relationship between glucose metabolism reprogramming of immune effector cells, such as T-cells and NK cells, and tumor occurrence and development (Cong et al, 2018;Kang and Tang, 2020). In the past, glycometabolism-related genes have been used to evaluate the prognosis of patients with prostate cancer, gastric cancer, ovarian cancer, and lung adenocarcinoma (Huang et al, 2019;Liu et al, 2020;Zhang et al, 2021a;He et al, 2021). However, there is no prognostic model based on glycometabolism-related genes that evaluates the survival and immune-related characteristics of patients with HCC.…”

Section: Discussionmentioning

confidence: 99%

Glycometabolism-related gene signature of hepatocellular carcinoma predicts prognosis and guides immunotherapy

Liu

Wang

et al. 2022

Front. Cell Dev. Biol.

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Hepatocellular carcinoma (HCC) is a severe cancer endangering human health. We constructed a novel glycometabolism-related risk score to predict prognosis and immunotherapy strategies in HCC patients. The HCC data sets were obtained from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database, and the glycometabolism-related gene sets were obtained from the Molecular Signature Database. The least absolute contraction and selection operator (LASSO) regression model was used to construct a risk score based on glycometabolism-related genes. A simple visual nomogram model with clinical indicators was constructed and its effectiveness in calibration, accuracy, and clinical value was evaluated. We also explored the correlation between glycometabolism-related risk scores and molecular pathways, immune cells, and functions. Patients in the low-risk group responded better to anti-CTLA-4 immune checkpoint treatment and benefited from immune checkpoint inhibitor (ICI) therapy. The study found that glycometabolism-related risk score can effectively distinguish the prognosis, molecular and immune-related characteristics of HCC patients, and may provide a new strategy for individualized treatment.

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Section: Discussionmentioning

confidence: 99%

Glycometabolism-related gene signature of hepatocellular carcinoma predicts prognosis and guides immunotherapy

Liu

Wang

et al. 2022

Front. Cell Dev. Biol.

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“…In addition, IL-3 secreted by YAP1 overexpressed GC can polarize macrophages into an M2-like phenotype and induce a GLUT3-dependent glycolysis program. At the same time, polarized M2 macrophages enhance the resistance of tumor cells to 5-FU (The antimetabolite 5-fluorouracil) by secreting CCL8 and activating the phosphorylation of JAK1/STAT3 signaling pathway [ 58 ].…”

Section: Metabolic Changes In the Microenvironment Of Gcmentioning

confidence: 99%

Impacts and mechanisms of metabolic reprogramming of tumor microenvironment for immunotherapy in gastric cancer

et al. 2022

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Metabolic disorders and abnormal immune function changes occur in tumor tissues and cells to varying degrees. There is increasing evidence that reprogrammed energy metabolism contributes to the development of tumor suppressive immune microenvironment and influences the course of gastric cancer (GC). Current studies have found that tumor microenvironment (TME) also has important clinicopathological significance in predicting prognosis and therapeutic efficacy. Novel approaches targeting TME therapy, such as immune checkpoint blockade (ICB), metabolic inhibitors and key enzymes of immune metabolism, have been involved in the treatment of GC. However, the interaction between GC cells metabolism and immune metabolism and how to make better use of these immunotherapy methods in the complex TME in GC are still being explored. Here, we discuss how metabolic reprogramming of GC cells and immune cells involved in GC immune responses modulate anti-tumor immune responses, as well as the effects of gastrointestinal flora in TME and GC. It is also proposed how to enhance anti-tumor immune response by understanding the targeted metabolism of these metabolic reprogramming to provide direction for the treatment and prognosis of GC.

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“…PTEN-induced kinase 1 (PINK1) deficiency in GC causes M2 polarization of TAMs, which is mainly related to the enhanced glycolysis level caused by PINK1 deletion ( 74 ). GC cells overexpressing YAP1 can promote M2 polarization by secreting IL-13, which activates the glucose transporter 3 (GLUT3) dependent glycolytic metabolic reprogramming of TAMs ( 75 , 76 ). While lactate can further promote the M2 polarization of TAM, inhibition of monocarboxylate transporters (MCT) or HIF-1α can significantly reverse this effect ( 77 ), hypoxia-induced elevated glycolysis levels can also induce a decrease in M1 macrophages in GC ( 78 ), which suggests an important role of glucose metabolism reprogramming in the tumor microenvironment.…”

Section: Metabolic Heterogeneity Gc Tmementioning

confidence: 99%

Tumor microenvironment-mediated immune tolerance in development and treatment of gastric cancer

Liu

et al. 2022

Front. Immunol.

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Tumor microenvironment is the general term for all non-cancer components and their metabolites in tumor tissue. These components include the extracellular matrix, fibroblasts, immune cells, and endothelial cells. In the early stages of tumors, the tumor microenvironment has a tumor suppressor function. As the tumor progresses, tumor immune tolerance is induced under the action of various factors, such that the tumor suppressor microenvironment is continuously transformed into a tumor-promoting microenvironment, which promotes tumor immune escape. Eventually, tumor cells manifest the characteristics of malignant proliferation, invasion, metastasis, and drug resistance. In recent years, stress effects of the extracellular matrix, metabolic and phenotypic changes of innate immune cells (such as neutrophils, mast cells), and adaptive immune cells in the tumor microenvironment have been revealed to mediate the emerging mechanisms of immune tolerance, providing us with a large number of emerging therapeutic targets to relieve tumor immune tolerance. Gastric cancer is one of the most common digestive tract malignancies worldwide, whose mortality rate remains high. According to latest guidelines, the first-line chemotherapy of advanced gastric cancer is the traditional platinum and fluorouracil therapy, while immunotherapy for gastric cancer is extremely limited, including only Human epidermal growth factor receptor 2 (HER-2) and programmed death ligand 1 (PD-L1) targeted drugs, whose benefits are limited. Clinical experiments confirmed that cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), vascular endothelial growth factor receptor (VEGFR) and other targeted drugs alone or in combination with other drugs have limited efficacy in patients with advanced gastric cancer, far less than in lung cancer, colon cancer, and other tumors. The failure of immunotherapy is mainly related to the induction of immune tolerance in the tumor microenvironment of gastric cancer. Therefore, solving the immune tolerance of tumors is key to the success of gastric cancer immunotherapy. In this study, we summarize the latest mechanisms of various components of the tumor microenvironment in gastric cancer for inducing immune tolerance and promoting the formation of the malignant phenotype of gastric cancer, as well as the research progress of targeting the tumor microenvironment to overcome immune tolerance in the treatment of gastric cancer.

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Yes associated protein 1 promotes resistance to 5-fluorouracil in gastric cancer by regulating GLUT3-dependent glycometabolism reprogramming of tumor-associated macrophages

Cited by 32 publications

References 37 publications

Glycometabolism-related gene signature of hepatocellular carcinoma predicts prognosis and guides immunotherapy

Glycometabolism-related gene signature of hepatocellular carcinoma predicts prognosis and guides immunotherapy

Impacts and mechanisms of metabolic reprogramming of tumor microenvironment for immunotherapy in gastric cancer

Tumor microenvironment-mediated immune tolerance in development and treatment of gastric cancer

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