Increased tumor glycolysis is associated with decreased immune infiltration across human solid tumors

Cohen, Ilan; Pareja, Fresia; Socci, Nicholas D.; Shen, Ronglai; Doane, Ashley S.; Schwartz, Jazmin; Khanin, Raya; Morris, Elizabeth A.; Sutton, Elizabeth; Blasberg, Ronald G.

doi:10.3389/fimmu.2022.880959

Cited by 8 publications

(6 citation statements)

References 104 publications

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“…Interestingly, previous studies have found that the expression of tumor glycolysis-related genes is inversely associated with immune-related genes in multiple solid tumor types. High tumor glycolysis is associated with low immune infiltration and poor prognosis 50 . A plethora of empirical evidence robustly substantiates the conjecture that the intricacy and variety inherent in the tumor microenvironment's immune milieu possesses the capacity to significantly impact both tumorigenesis and metastasis.…”

Section: Discussionmentioning

confidence: 99%

TRIP6 a potential diagnostic marker for colorectal cancer with glycolysis and immune infiltration association

Liu,

Chen,

Wan

et al. 2024

Sci Rep

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Thyroid hormone receptor interactor 6 (TRIP6) it is an adaptor protein belonging to the zyxin family of LIM proteins, participating in signaling events through interactions with various molecules. Despite this, TRIP6's role in colorectal cancer (CRC), particularly its correlation with glucose metabolism and immune cell infiltration, remains unclear. Through the TCGA and GEO databases, we obtained RNA sequencing data to facilitate our in-depth study and analysis of TRIP6 expression. To investigate the prognostic value of TRIP6 in CRC, we also used univariate Cox regression analysis. In addition, this study also covered a series of analyses, including clinicopathological analysis, functional enrichment analysis, glycolysis correlation analysis, immunoinfiltration analysis, immune checkpoint analysis, and angiogenesis correlation analysis, to gain a comprehensive and in-depth understanding of this biological phenomenon. It has been found that TRIP6 expression is significantly upregulated in CRC and correlates with the stage of the disease. Its overexpression portends a worse survival time. Functional enrichment analysis reveals that TRIP6 is associated with focal adhesion and glycolysis. Mechanistically, TRIP6 appears to exert its tumorigenic effect by regulating the glycolysis-related gene GPI. A higher level of expression of TRIP6 is associated with an increase in the number of iDC immune cells and a decrease in the number of Th1 immune cells. Also, TRIP6 may promote angiogenesis in tumor cells by promoting the expression of JAG2. Our study uncovers the upregulation of TRIP6 in CRC, illuminating its prognostic and diagnostic value within this context. Furthermore, we examine the relationship between TRIP6 expression levels, glycolysis, angiogenesis and immune cell infiltration. This underscores its potential as a biomarker for CRC treatment and as a therapeutic target.

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Section: Discussionmentioning

confidence: 99%

TRIP6 a potential diagnostic marker for colorectal cancer with glycolysis and immune infiltration association

Liu,

Chen,

Wan

et al. 2024

Sci Rep

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“…Of interest is an apparent trend in the glycolytic phenotype being the most sensitive or responsive to autophagic inhibition. It has been presented as a consistent predictor in blood cancers ( Chen et al, 2014b ) and solid tumours ( Cohen et al, 2022 ). However, it is suggested efficacy would be increased as an adjuvant with some of the frontline chemotherapeutics that result in a shift in metabolic programming as a means of evading their effects, such as Cisplatin ( Xu et al, 2022 ), 5FU ( Denise et al, 2015 ) and Doxorubicin ( McGuirk et al, 2021 ).…”

Section: Discussion/conclusionmentioning

confidence: 99%

Inhibition of autophagy; an opportunity for the treatment of cancer resistance

Tonkin-Reeves,

Giuliani,

Price

2023

Front. Cell Dev. Biol.

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The process of macroautophagy plays a pivotal role in the degradation of long-lived, superfluous, and damaged proteins and organelles, which are later recycled for cellular use. Normal cells rely on autophagy to combat various stressors and insults to ensure survival. However, autophagy is often upregulated in cancer cells, promoting a more aggressive phenotype that allows mutated cells to evade death after exposure to therapeutic treatments. As a result, autophagy has emerged as a significant factor in therapeutic resistance across many cancer types, with underlying mechanisms such as DNA damage, cell cycle arrest, and immune evasion. This review provides a comprehensive summary of the role of autophagy in therapeutic resistance and the limitations of available autophagic inhibitors in cancer treatment. It also highlights the urgent need to explore new inhibitors that can synergize with existing therapies to achieve better patient treatment outcomes. Advancing research in this field is crucial for developing more effective treatments that can help improve the lives of cancer patients.

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“…In TME, whether oxygen is sufficient or not, tumor cells make use of plenty of glucose for glycolysis to generate lactic acid (30)(31)(32). As we all know, hypoxia-inducible factor-1 (HIF-1) induced by hypoxia can determine the modes of glucose metabolism, and a variety of substances in TME increase the amount of HIF-1 protein and also promote glycolysis (30).…”

Section: Glucose Metabolismmentioning

confidence: 99%

Analyzing the impact of metabolism on immune cells in tumor microenvironment to promote the development of immunotherapy

Long,

Shi,

et al. 2024

Front. Immunol.

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Tumor metabolism and tumor immunity are inextricably linked. Targeting the metabolism of tumors is a point worth studying in tumor immunotherapy. Recently, the influence of the metabolism of tumors and immune cells on the occurrence, proliferation, metastasis, and prognosis of tumors has attracted more attention. Tumor tissue forms a specific tumor microenvironment (TME). In addition to tumor cells, there are also immune cells, stromal cells, and other cells in TME. To adapt to the environment, tumor cells go through the metabolism reprogramming of various substances. The metabolism reprogramming of tumor cells may further affect the formation of the tumor microenvironment and the function of a variety of cells, especially immune cells, eventually promoting tumor development. Therefore, it is necessary to study the metabolism of tumor cells and its effects on immune cells to guide tumor immunotherapy. Inhibiting tumor metabolism may restore immune balance and promote the immune response in tumors. This article will describe glucose metabolism, lipid metabolism, amino acid metabolism, and immune cells in tumors. Besides, the impact of metabolism on the immune cells in TME is also discussed for analyzing and exploring tumor immunotherapy.

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Increased tumor glycolysis is associated with decreased immune infiltration across human solid tumors

Cited by 8 publications

References 104 publications

TRIP6 a potential diagnostic marker for colorectal cancer with glycolysis and immune infiltration association

TRIP6 a potential diagnostic marker for colorectal cancer with glycolysis and immune infiltration association

Inhibition of autophagy; an opportunity for the treatment of cancer resistance

Analyzing the impact of metabolism on immune cells in tumor microenvironment to promote the development of immunotherapy

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