Research on the Metabolism of Immune Cells and Immune Escape Mechanisms in the Tumor Immune Microenvironment

Authors

  • Ziyue Zhang

DOI:

https://doi.org/10.61173/p9x94b50

Keywords:

Tumor microenvironment, Immune cells, Immune escape, Immune cell metabolism, Mechanism of immune escape

Abstract

The tumor microenvironment (TME) is a complex and dynamic system consisting of tumor cells, immune cells, stromal cells, and extracellular matrix, whose internal metabolic state and other characteristics have a profound impact on the proliferation, invasion, metastasis and treatment response of tumors. Currently, there is a problem of poor treatment efficiency for tumors due to immune escape. So, analyzing the internal relationship between the metabolism of immune cells and the mechanism of immune escape in TME is a goal for improving treatment outcomes. This study involved analyzing the changes in immune cell metabolites and investigating the impact of metabolic pathways on immune function. Firstly, the metabolic changes of different immune cells (CD8⁺T cells, NK cells, Tregs, TAMs) were described, and it was found there was a significant metabolic disorder in TME. The reprogramming of sugar metabolism inhibits immune activity, the fatty acid metabolism promotes immune evasion, and the disorder of amino acid metabolism seizes key amino acids leading to the immune cells being in a “nutritional deficiency” state. Meanwhile, the abnormal accumulation of metabolites such as lactic acid and ketone bodies jointly creates an immunosuppressive microenvironment. However, some immune functions can be restored and the growth of tumors can be inhibited by regulating certain metabolic pathways. Treating the metabolic disorders in TME is expected to become a breakthrough in tumor immune suppression. It provides experimental evidence for developing the combined strategy of “metabolic regulation + immunotherapy” and opens up a new direction for the design of tumor treatment plans.

References

[1] Xue Yaqi, Qin Liqiang, and Zhang Jianwei. Research P r o g r e s s o n A m i n o . A c i d M e t a b o l i s m i n Tu m o r Microenvironment. Journal of Tumor Metabolism and Nutrition, 2024. 11(06): p. 756-762.

[2] Zi Tong, Wu Denglong, and Wu Gang. Research Progress of Glycolysis. in. Prostate Cancer. Journal of Tongji University (Medical Edition), 2024. 45(05): p. 777-784.

[3] Zhang Yesheng, et al. Research Progress on the Regulation of Tumor. Cell Drug Resistance by Immune Cells in Tumor Microenvironment. Journal of Shanghai Jiao Tong University (Medical Edition), 2024. 44(07): p. 830-838.

[4] Du Naiwen, Bailing, and Cui Jiowei. Mechanisms of Tumor Immune. Escape and Therapeutic Strategies. Chinese Journal of Tumor Biotherapy, 2019. 26(04): p. 454-462.

[5] Cao Meng, et al. Research Progress on the Role of Metabolic. Reprogramming of Macrophages in Infection and Tumor Development. Cancer Progression, Alteration and Mutation, 2025. 37(03): p. 262-265.

[6] Arneth, B., Tumor Microenvironment. Medicina (Kaunas), 2019. 56(1).

[7] Feng Xili, et al. Role of Natural Killer Cells in Anti-Infection and Tumor. Therapy. Journal of Cell and Molecular Immunology, 2023. 39(10): p. 952-958.

[8] Hsieh, C.S., H.M. Lee, and C.W. Lio, Selection of regulatory T cells in the thymus. Nat Rev Immunol, 2012. 12(3): p. 157-67.

[9] Su Jialin, et al., Research Progress on Metabolic Reprogramming of. Tumor-Infiltrating T Lymphocytes and Immune Resistance. Chinese Journal of Oncology, 2024. 51(07): p. 366-371.

[10] Olkhanud, P.B., et al., Tumor-evoked regulatory B cells promote breast cancer metastasis by converting resting CD4⁺ T cells to T-regulatory cells. Cancer Res, 2011. 71(10): p. 3505-15.

[11] Shi, J., et al., Characterization of glycometabolism and tumor immune microenvironment for predicting clinical outcomes in gastric cancer. iScience, 2023. 26(3): p. 106214.

[12] Anderson, N.M., et al., The emerging role and targetability of the TCA cycle in cancer metabolism. Protein Cell, 2018. 9(2): p. 216-237.

[13] Bian, X., et al., Lipid metabolism and cancer. J Exp Med, 2021. 218(1).

[14] De Martino, M., et al., Cancer cell metabolism and antitumour immunity. Nat Rev Immunol, 2024. 24(9): p. 654- 669.

[15] Edwards, D.N., et al., Selective glutamine metabolism inhibition in tumor cells improves antitumor T lymphocyte activity in triple-negative breast cancer. J Clin Invest, 2021. 131(4).

[16] Bian, Y., et al., Cancer SLC43A2 alters T cell methionine metabolism and histone methylation. Nature, 2020. 585(7824): p. 277-282.

[17] Cao, J. and Q. Yan, Cancer Epigenetics, Tumor Immunity, and Immunotherapy. Trends Cancer, 2020. 6(7): p. 580-592.

[18] Vinay, D.S., et al., Immune evasion in cancer: Mechanistic basis and therapeutic strategies. Semin Cancer Biol, 2015. 35 Suppl: p. S185-s198.

[19] Luo, Y., et al., Neoadjuvant PARPi or chemotherapy in ovarian cancer informs targeting effector Treg cells for homologous-recombination-deficient tumors. Cell, 2024. 187(18): p. 4905-4925.e24.

[20] Yen, K.E., et al., Cancer-associated IDH mutations: biomarker and therapeutic opportunities. Oncogene, 2010. 29(49): p. 6409-17.

[21] Abdel-Rahman, O., Statin treatment and outcomes of metastatic pancreatic cancer: a pooled analysis of two phase III studies. Clin Transl Oncol, 2019. 21(6): p. 810-816.

[22] Kim, S.T., et al., Simvastatin plus capecitabine-cisplatin versus placebo plus capecitabine-cisplatin in patients with previously untreated advanced gastric cancer: a double-blind randomised phase 3 study. Eur J Cancer, 2014. 50(16): p. 2822- 30.

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Published

2025-12-19