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Review
. 2022 Dec 12:13:1038650.
doi: 10.3389/fimmu.2022.1038650. eCollection 2022.

Glucose metabolism and tumour microenvironment in pancreatic cancer: A key link in cancer progression

Shi Dong  1 , Wancheng Li  1 , Xin Li  2 , Zhengfeng Wang  3 , Zhou Chen  2 , Huaqing Shi  1 , Ru He  2 , Chen Chen  2 , Wence Zhou  4
Affiliations
Review

Glucose metabolism and tumour microenvironment in pancreatic cancer: A key link in cancer progression

Shi Dong et al. Front Immunol. .

Abstract

Early and accurate diagnosis and treatment of pancreatic cancer (PC) remain challenging endeavors globally. Late diagnosis lag, high invasiveness, chemical resistance, and poor prognosis are unresolved issues of PC. The concept of metabolic reprogramming is a hallmark of cancer cells. Increasing evidence shows that PC cells alter metabolic processes such as glucose, amino acids, and lipids metabolism and require continuous nutrition for survival, proliferation, and invasion. Glucose metabolism, in particular, regulates the tumour microenvironment (TME). Furthermore, the link between glucose metabolism and TME also plays an important role in the targeted therapy, chemoresistance, radiotherapy ineffectiveness, and immunosuppression of PC. Altered metabolism with the TME has emerged as a key mechanism regulating PC progression. This review shed light on the relationship between TME, glucose metabolism, and various aspects of PC. The findings of this study provide a new direction in the development of PC therapy targeting the metabolism of cancer cells.

Keywords: glucose metabolism; pancreatic cancer; prognosis; treatment; tumour microenvironment.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Aerobic glycolysis in PC. The entire process of glucose uptake and conversion and utilization through a series of pathways, including aerobic glycolysis pathway to generate lactate and ATP, PPP pathway to generate 5-phosphate ribose, serine pathway to generate Gly and Leu and hexosamine biosynthesis pathway to generate O-GlcNAc is shown.
Figure 2
Figure 2
Metabolic crosstalk between PC cells and the TME. The figure completely shows the roles and pathways of important components in the TME in the glycolytic process, proliferation, and invasion of PC, including CAFs, TAMs, DCs, neutrophils, NK cells, Tregs, Bregs, endothelial cells, MDSCs, and microbiota.
Figure 3
Figure 3
The association between PC glycolysis and ferroptosis and TME. The NAPDH that is produced by the PPP pathway in PC cells provides sufficient reducing equivalents for the synthesis of GSH. In addition, a large amount of lactate produced by the glycolytic pathway in cancer cells and TME undergoes a series of enzymatic reactions to generate MUFA, which reduces ferroptosis occurrence. However, the IFN-γ derived from CD8(+) T cells in the TME induces ferroptosis by inhibiting system Xc-, thereby suppressing malignant progression of PC.
Figure 4
Figure 4
Schematic presentation of immune aging in PC. In a normal PC microenvironment, due to the presence of anti-tumour immune cells such as NK cells, the proliferation, invasion and vascular invasion of cancer cells are inhibited. However, in the immunosenescence microenvironment, the tumour suppressive abilities of immune cells are weakened, and rapid proliferation of cancer cells simultaneously induces massive infiltration of cancer-promoting immune cells, including Tregs as well as TAMs, and promotes cancer cell vascular invasion and distant metastasis.
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