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Review
. 2023 Dec 5;45(12):9753-9767.
doi: 10.3390/cimb45120609.

Metabolic Interplay in the Tumor Microenvironment: Implications for Immune Function and Anticancer Response

Reem Youssef  1 , Rohan Maniar  2 , Jaffar Khan  1 , Hector Mesa  1
Affiliations
Review

Metabolic Interplay in the Tumor Microenvironment: Implications for Immune Function and Anticancer Response

Reem Youssef et al. Curr Issues Mol Biol. .

Abstract

Malignant tumors exhibit rapid growth and high metabolic rates, similar to embryonic stem cells, and depend on aerobic glycolysis, known as the "Warburg effect". This understanding has enabled the use of radiolabeled glucose analogs in tumor staging and therapeutic response assessment via PET scans. Traditional treatments like chemotherapy and radiotherapy target rapidly dividing cells, causing significant toxicity. Despite immunotherapy's impact on solid tumor treatment, gaps remain, leading to research on cancer cell evasion of immune response and immune tolerance induction via interactions with the tumor microenvironment (TME). The TME, consisting of immune cells, fibroblasts, vessels, and the extracellular matrix, regulates tumor progression and therapy responses. TME-targeted therapies aim to transform this environment from supporting tumor growth to impeding it and fostering an effective immune response. This review examines the metabolic disparities between immune cells and cancer cells, their impact on immune function and therapeutic targeting, the TME components, and the complex interplay between cancer cells and nontumoral cells. The success of TME-targeted therapies highlights their potential to achieve better cancer control or even a cure.

Keywords: immunotherapy; oncometabolites; tumor microenvironment.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Tumor-immune microenvironment. (A) Warburg effect: Positron emission tomography visualizes a tongue base carcinoma (upper arrowhead) and neck lymph node metastasis (lower arrowhead) using radioactive glucose analogs. (B) Cancer-associated inflammation: The image exhibits mononuclear leukocytes (lymphocytes, histiocytes, plasma cells), multinucleated giant cells, and polymorphonuclear leukocytes (PMN) closely intertwined with tumor cells. Despite the prevalent presence of inflammatory cells in most tumors, the immune response tends toward immune tolerance (Hematoxylin and Eosin, 40× magnification).
See this image and copyright information in PMC

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