Contradictory Roles of Lipid Metabolism in Immune Response Within the Tumor Microenvironment

Overview

Journal J Hematol Oncol

Publisher Biomed Central

Specialties Hematology
Oncology

Date 2021 Nov 7

PMID 34742349

Citations 83

Authors

Weina Yu

Qingyang Lei

Li Yang

Guohui Qin

Shasha Liu

Dan Wang

Yu Ping

Yi Zhang

Affiliations

Soon will be listed here.

Abstract

Complex interactions between the immune system and tumor cells exist throughout the initiation and development of cancer. Although the immune system eliminates malignantly transformed cells in the early stage, surviving tumor cells evade host immune defense through various methods and even reprogram the anti-tumor immune response to a pro-tumor phenotype to obtain unlimited growth and metastasis. The high proliferation rate of tumor cells increases the demand for local nutrients and oxygen. Poorly organized vessels can barely satisfy this requirement, which results in an acidic, hypoxic, and glucose-deficient tumor microenvironment. As a result, lipids in the tumor microenvironment are activated and utilized as a primary source of energy and critical regulators in both tumor cells and related immune cells. However, the exact role of lipid metabolism reprogramming in tumor immune response remains unclear. A comprehensive understanding of lipid metabolism dysfunction in the tumor microenvironment and its dual effects on the immune response is critical for mapping the detailed landscape of tumor immunology and developing specific treatments for cancer patients. In this review, we have focused on the dysregulation of lipid metabolism in the tumor microenvironment and have discussed its contradictory roles in the tumor immune response. In addition, we have summarized the current therapeutic strategies targeting lipid metabolism in tumor immunotherapy. This review provides a comprehensive summary of lipid metabolism in the tumor immune response.

Citing Articles

Lipid metabolic reprograming: the unsung hero in breast cancer progression and tumor microenvironment.

Wan M, Pan S, Shan B, Diao H, Jin H, Wang Z Mol Cancer. 2025; 24(1):61.

PMID: 40025508 PMC: 11874147. DOI: 10.1186/s12943-025-02258-1.

Comprehensive analysis of lipid metabolic signatures identified CEBPD promotes breast cancer cell proliferation.

Zhao Y, He H, Huang L, Yu L Sci Rep. 2025; 15(1):6570.

PMID: 39994306 PMC: 11850814. DOI: 10.1038/s41598-025-90869-5.

Investigating the causal relationship between the plasma lipidome and cholangiocarcinoma mediated by immune cells: a mediation Mendelian randomization study.

Yin H, Yang K, Lou Y, Zhao Y Sci Rep. 2025; 15(1):5807.

PMID: 39962308 PMC: 11832772. DOI: 10.1038/s41598-025-90140-x.

The role of ubiquitination and deubiquitination in cancer lipid metabolism.

Xu Y, Zeng J, Fu S, Liu K, Mao Y, Tao S Front Oncol. 2025; 15:1464914.

PMID: 39944823 PMC: 11813751. DOI: 10.3389/fonc.2025.1464914.

Serum Lipid Biomarkers and the Risk of Gastrointestinal Cancers in a Chinese Population: The Kailuan Prospective Study.

Xiao Y, Du X, Wang T, Liu D, You H, Wang H Cancer Med. 2025; 14(3):e70654.

PMID: 39912426 PMC: 11799922. DOI: 10.1002/cam4.70654.

References

Kawalekar O, OConnor R, Fraietta J, Guo L, McGettigan S, Posey Jr A . Distinct Signaling of Coreceptors Regulates Specific Metabolism Pathways and Impacts Memory Development in CAR T Cells. Immunity. 2016; 44(2):380-90. DOI: 10.1016/j.immuni.2016.01.021. View

Lombardo D, Guy O . Studies on the substrate specificity of a carboxyl ester hydrolase from human pancreatic juice. II. Action on cholesterol esters and lipid-soluble vitamin esters. Biochim Biophys Acta. 1980; 611(1):147-55. DOI: 10.1016/0005-2744(80)90050-9. View

Yang Z, Guo J, Weng L, Tang W, Jin S, Ma W . Myeloid-derived suppressor cells-new and exciting players in lung cancer. J Hematol Oncol. 2020; 13(1):10. PMC: 6995114. DOI: 10.1186/s13045-020-0843-1. View

Schlager S, Madden L, Meltzer M, Bara S, Mamula M . Role of macrophage lipids in regulating tumoricidal activity. Cell Immunol. 1983; 77(1):52-68. DOI: 10.1016/0008-8749(83)90006-0. View

Jin S, Yang Z, Hao X, Tang W, Ma W, Zong H . Roles of HMGB1 in regulating myeloid-derived suppressor cells in the tumor microenvironment. Biomark Res. 2020; 8:21. PMC: 7298841. DOI: 10.1186/s40364-020-00201-8. View

Guo C, Yi H, Yu X, Zuo D, Qian J, Yang G . In situ vaccination with CD204 gene-silenced dendritic cell, not unmodified dendritic cell, enhances radiation therapy of prostate cancer. Mol Cancer Ther. 2012; 11(11):2331-41. PMC: 3496075. DOI: 10.1158/1535-7163.MCT-12-0164. View

Martin S . Caveolae, lipid droplets, and adipose tissue biology: pathophysiological aspects. Horm Mol Biol Clin Investig. 2014; 15(1):11-8. DOI: 10.1515/hmbci-2013-0035. View

Yao C, Fowle-Grider R, Mahieu N, Liu G, Chen Y, Wang R . Exogenous Fatty Acids Are the Preferred Source of Membrane Lipids in Proliferating Fibroblasts. Cell Chem Biol. 2016; 23(4):483-93. PMC: 5510604. DOI: 10.1016/j.chembiol.2016.03.007. View

Buhman K, Accad M, Novak S, Choi R, Wong J, Hamilton R . Resistance to diet-induced hypercholesterolemia and gallstone formation in ACAT2-deficient mice. Nat Med. 2000; 6(12):1341-7. DOI: 10.1038/82153. View

10.

Wu H, Weidinger C, Schmidt F, Keye J, Friedrich M, Yerinde C . Oleate but not stearate induces the regulatory phenotype of myeloid suppressor cells. Sci Rep. 2017; 7(1):7498. PMC: 5548895. DOI: 10.1038/s41598-017-07685-9. View

11.

Liu Y, Lu L, Wen D, Liu D, Dong L, Gao D . MiR-612 regulates invadopodia of hepatocellular carcinoma by HADHA-mediated lipid reprogramming. J Hematol Oncol. 2020; 13(1):12. PMC: 7006096. DOI: 10.1186/s13045-019-0841-3. View

12.

Li P, Lu M, Shi J, Gong Z, Hua L, Li Q . Lung mesenchymal cells elicit lipid storage in neutrophils that fuel breast cancer lung metastasis. Nat Immunol. 2020; 21(11):1444-1455. PMC: 7584447. DOI: 10.1038/s41590-020-0783-5. View

13.

Zhu H, Zhang Q, Chen G . CXCR6 deficiency ameliorates ischemia-reperfusion injury by reducing the recruitment and cytokine production of hepatic NKT cells in a mouse model of non-alcoholic fatty liver disease. Int Immunopharmacol. 2019; 72:224-234. DOI: 10.1016/j.intimp.2019.04.021. View

14.

Zhang Y, Sun Y, Rao E, Yan F, Li Q, Zhang Y . Fatty acid-binding protein E-FABP restricts tumor growth by promoting IFN-β responses in tumor-associated macrophages. Cancer Res. 2014; 74(11):2986-98. PMC: 4040301. DOI: 10.1158/0008-5472.CAN-13-2689. View

15.

Zhang Q, Wang H, Mao C, Sun M, Dominah G, Chen L . Fatty acid oxidation contributes to IL-1β secretion in M2 macrophages and promotes macrophage-mediated tumor cell migration. Mol Immunol. 2017; 94:27-35. PMC: 5801116. DOI: 10.1016/j.molimm.2017.12.011. View

16.

Farese Jr R, Walther T . Lipid droplets finally get a little R-E-S-P-E-C-T. Cell. 2009; 139(5):855-60. PMC: 3097139. DOI: 10.1016/j.cell.2009.11.005. View

17.

Yang L, Luo Q, Lu L, Zhu W, Sun H, Wei R . Increased neutrophil extracellular traps promote metastasis potential of hepatocellular carcinoma via provoking tumorous inflammatory response. J Hematol Oncol. 2020; 13(1):3. PMC: 6945602. DOI: 10.1186/s13045-019-0836-0. View

18.

Strauss L, Mahmoud M, Weaver J, Tijaro-Ovalle N, Christofides A, Wang Q . Targeted deletion of PD-1 in myeloid cells induces antitumor immunity. Sci Immunol. 2020; 5(43). PMC: 7183328. DOI: 10.1126/sciimmunol.aay1863. View

19.

Zeyda M, Saemann M, Stuhlmeier K, Mascher D, Nowotny P, Zlabinger G . Polyunsaturated fatty acids block dendritic cell activation and function independently of NF-kappaB activation. J Biol Chem. 2005; 280(14):14293-301. DOI: 10.1074/jbc.M410000200. View

20.

Hatzivassiliou G, Zhao F, Bauer D, Andreadis C, Shaw A, Dhanak D . ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell. 2005; 8(4):311-21. DOI: 10.1016/j.ccr.2005.09.008. View