The Role of Lipid Metabolism in Tumor Immune Microenvironment and Potential Therapeutic Strategies

Overview

Journal Front Oncol

Specialty Oncology

Date 2022 Sep 29

PMID 36172157

Authors

Danting Wang

Qizhen Ye

Haochen Gu

Zhigang Chen

Affiliations

Soon will be listed here.

Abstract

Aberrant lipid metabolism is nonnegligible for tumor cells to adapt to the tumor microenvironment (TME). It plays a significant role in the amount and function of immune cells, including tumor-associated macrophages, T cells, dendritic cells and marrow-derived suppressor cells. It is well-known that the immune response in TME is suppressed and lipid metabolism is closely involved in this process. Immunotherapy, containing anti-PD1/PDL1 therapy and adoptive T cell therapy, is a crucial clinical cancer therapeutic strategy nowadays, but they display a low-sensibility in certain cancers. In this review, we mainly discussed the importance of lipid metabolism in the formation of immunosuppressive TME, and explored the effectiveness and sensitivity of immunotherapy treatment by regulating the lipid metabolism.

Citing Articles

Lipid Metabolism in Breast Cancer: From Basic Research to Clinical Application.

Huang X, Liu B, Shen S Cancers (Basel). 2025; 17(4).

PMID: 40002245 PMC: 11852908. DOI: 10.3390/cancers17040650.

Lipids in the tumor microenvironment: immune modulation and metastasis.

Pascual G, Benitah S Front Oncol. 2024; 14:1435480.

PMID: 39391242 PMC: 11464260. DOI: 10.3389/fonc.2024.1435480.

IGFBP1 promotes the proliferation and migration of lung adenocarcinoma cells through the PPARα pathway.

Li Y, Yang X, Han T, Zhou J, Liu Y, Guo J Transl Oncol. 2024; 49:102095.

PMID: 39167955 PMC: 11382126. DOI: 10.1016/j.tranon.2024.102095.

A promising anti-tumor targeting on ERMMDs mediated abnormal lipid metabolism in tumor cells.

Pang M, Yu L, Li X, Lu C, Xiao C, Liu Y Cell Death Dis. 2024; 15(8):562.

PMID: 39098929 PMC: 11298533. DOI: 10.1038/s41419-024-06956-4.

Triple Negative Breast Cancer: Molecular Subtype-Specific Immune Landscapes with Therapeutic Implications.

Syrnioti A, Petousis S, Newman L, Margioula-Siarkou C, Papamitsou T, Dinas K Cancers (Basel). 2024; 16(11).

PMID: 38893213 PMC: 11171372. DOI: 10.3390/cancers16112094.

References

Camarda R, Zhou A, Kohnz R, Balakrishnan S, Mahieu C, Anderton B . Inhibition of fatty acid oxidation as a therapy for MYC-overexpressing triple-negative breast cancer. Nat Med. 2016; 22(4):427-32. PMC: 4892846. DOI: 10.1038/nm.4055. View

Zaugg K, Yao Y, Reilly P, Kannan K, Kiarash R, Mason J . Carnitine palmitoyltransferase 1C promotes cell survival and tumor growth under conditions of metabolic stress. Genes Dev. 2011; 25(10):1041-51. PMC: 3093120. DOI: 10.1101/gad.1987211. View

Pike L, Smift A, Croteau N, Ferrick D, Wu M . Inhibition of fatty acid oxidation by etomoxir impairs NADPH production and increases reactive oxygen species resulting in ATP depletion and cell death in human glioblastoma cells. Biochim Biophys Acta. 2011; 1807(6):726-34. DOI: 10.1016/j.bbabio.2010.10.022. View

Piccinin E, Cariello M, Moschetta A . Lipid metabolism in colon cancer: Role of Liver X Receptor (LXR) and Stearoyl-CoA Desaturase 1 (SCD1). Mol Aspects Med. 2020; 78:100933. DOI: 10.1016/j.mam.2020.100933. View

Hinshaw D, Shevde L . The Tumor Microenvironment Innately Modulates Cancer Progression. Cancer Res. 2019; 79(18):4557-4566. PMC: 6744958. DOI: 10.1158/0008-5472.CAN-18-3962. View

Zhang C, Liu J, Huang G, Zhao Y, Yue X, Wu H . Cullin3-KLHL25 ubiquitin ligase targets ACLY for degradation to inhibit lipid synthesis and tumor progression. Genes Dev. 2016; 30(17):1956-70. PMC: 5066239. DOI: 10.1101/gad.283283.116. View

Luo J, Yang H, Song B . Mechanisms and regulation of cholesterol homeostasis. Nat Rev Mol Cell Biol. 2019; 21(4):225-245. DOI: 10.1038/s41580-019-0190-7. View

Zhou T, Zhan J, Fang W, Zhao Y, Yang Y, Hou X . Serum low-density lipoprotein and low-density lipoprotein expression level at diagnosis are favorable prognostic factors in patients with small-cell lung cancer (SCLC). BMC Cancer. 2017; 17(1):269. PMC: 5391547. DOI: 10.1186/s12885-017-3239-z. View

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

10.

Yu W, Lei Q, Yang L, Qin G, Liu S, Wang D . Contradictory roles of lipid metabolism in immune response within the tumor microenvironment. J Hematol Oncol. 2021; 14(1):187. PMC: 8572421. DOI: 10.1186/s13045-021-01200-4. View

11.

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

12.

Choi H, Ha S, Kim H, Ahn S, Kang M, Kim K . The prognostic effects of tumor infiltrating regulatory T cells and myeloid derived suppressor cells assessed by multicolor flow cytometry in gastric cancer patients. Oncotarget. 2016; 7(7):7940-51. PMC: 4884965. DOI: 10.18632/oncotarget.6958. View

13.

Corral-Jara K, da Silva G, Fierro N, Soumelis V . Modeling the Th17 and Tregs Paradigm: Implications for Cancer Immunotherapy. Front Cell Dev Biol. 2021; 9:675099. PMC: 8137995. DOI: 10.3389/fcell.2021.675099. View

14.

Niu Z, Shi Q, Zhang W, Shu Y, Yang N, Chen B . Caspase-1 cleaves PPARγ for potentiating the pro-tumor action of TAMs. Nat Commun. 2017; 8(1):766. PMC: 5626701. DOI: 10.1038/s41467-017-00523-6. View

15.

Alwarawrah Y, Hughes P, Loiselle D, Carlson D, Darr D, Jordan J . Fasnall, a Selective FASN Inhibitor, Shows Potent Anti-tumor Activity in the MMTV-Neu Model of HER2(+) Breast Cancer. Cell Chem Biol. 2016; 23(6):678-88. PMC: 6443244. DOI: 10.1016/j.chembiol.2016.04.011. View

16.

Luis G, Godfroid A, Nishiumi S, Cimino J, Blacher S, Maquoi E . Tumor resistance to ferroptosis driven by Stearoyl-CoA Desaturase-1 (SCD1) in cancer cells and Fatty Acid Biding Protein-4 (FABP4) in tumor microenvironment promote tumor recurrence. Redox Biol. 2021; 43:102006. PMC: 8163990. DOI: 10.1016/j.redox.2021.102006. View

17.

Stopsack K, Gerke T, Sinnott J, Penney K, Tyekucheva S, Sesso H . Cholesterol Metabolism and Prostate Cancer Lethality. Cancer Res. 2016; 76(16):4785-90. PMC: 4987257. DOI: 10.1158/0008-5472.CAN-16-0903. View

18.

Yang X, Lu Y, Hang J, Zhang J, Zhang T, Huo Y . Lactate-Modulated Immunosuppression of Myeloid-Derived Suppressor Cells Contributes to the Radioresistance of Pancreatic Cancer. Cancer Immunol Res. 2020; 8(11):1440-1451. DOI: 10.1158/2326-6066.CIR-20-0111. View

19.

Wang F, Lau J, Yu J . The role of natural killer cell in gastrointestinal cancer: killer or helper. Oncogene. 2020; 40(4):717-730. PMC: 7843415. DOI: 10.1038/s41388-020-01561-z. View

20.

Boutilier A, Elsawa S . Macrophage Polarization States in the Tumor Microenvironment. Int J Mol Sci. 2021; 22(13). PMC: 8268869. DOI: 10.3390/ijms22136995. View