Lipid Metabolism and Tumor Immunotherapy

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2023 Jun 1

PMID 37261073

Authors

Yue Wang

Zongjin Guo

Adamu Danbala Isah

Shuangwei Chen

Yongfei Ren

Huazhong Cai

Affiliations

Soon will be listed here.

Abstract

In recent years, the relationship between lipid metabolism and tumour immunotherapy has been thoroughly investigated. An increasing number of studies have shown that abnormal gene expression and ectopic levels of metabolites related to fatty acid synthesis or fatty acid oxidation affect tumour metastasis, recurrence, and drug resistance. Tumour immunotherapy that aims to promote an antitumour immune response has greatly improved the outcomes for tumour patients. However, lipid metabolism reprogramming in tumour cells or tumour microenvironment-infiltrating immune cells can influence the antitumour response of immune cells and induce tumor cell immune evasion. The recent increase in the prevalence of obesity-related cancers has drawn attention to the fact that obesity increases fatty acid oxidation in cancer cells and suppresses the activation of immune cells, thereby weakening antitumour immunity. This article reviews the changes in lipid metabolism in cells in the tumour microenvironment and describes the relationship between lipid metabolism reprogramming in multiple cell types and tumour immunotherapy.

Citing Articles

Exploring causal relationship between the lipids, immune cells, and leiomyosarcoma: A Mendelian randomization and mediation analysis.

Jin X, Jiang C, Gan X, Zou X, Li H, Zhang L Medicine (Baltimore). 2025; 103(52):e40919.

PMID: 39969344 PMC: 11688058. DOI: 10.1097/MD.0000000000040919.

Fatty acid metabolism: A new target for nasopharyngeal carcinoma therapy.

Li J, Ping P, Li Y, Xu X Chin J Cancer Res. 2025; 36(6):652-668.

PMID: 39802901 PMC: 11724175. DOI: 10.21147/j.issn.1000-9604.2024.06.05.

Integrated bioinformatics reveals genetic links between visceral obesity and uterine tumors.

Samantaray S, Joshi N, Vasa S, Shibu S, Kaloni A, Parekh B Mol Genet Genomics. 2024; 299(1):93.

PMID: 39368016 DOI: 10.1007/s00438-024-02184-9.

TMEM147: A Promising Cancer Biomarker Associated with Immune Cell Infiltration and Prognosis in LIHC-Insights from a Comprehensive Pan-Cancer Genomic Analysis.

Li Y, Chen H, Zhang B, Liu J, Ma J, Ma W ACS Omega. 2024; 9(25):27137-27157.

PMID: 38947838 PMC: 11209882. DOI: 10.1021/acsomega.4c01215.

VLDL and LDL Subfractions Enhance the Risk Stratification of Individuals Who Underwent Epstein-Barr Virus-Based Screening for Nasopharyngeal Carcinoma: A Multicenter Cohort Study.

Zhou Z, Tang T, Li N, Zheng Q, Xiao T, Tian Y Adv Sci (Weinh). 2024; 11(22):e2308765.

PMID: 38520712 PMC: 11165512. DOI: 10.1002/advs.202308765.

References

Rosa Neto J, Calder P, Curi R, Newsholme P, Sethi J, Silveira L . The Immunometabolic Roles of Various Fatty Acids in Macrophages and Lymphocytes. Int J Mol Sci. 2021; 22(16). PMC: 8395092. DOI: 10.3390/ijms22168460. View

Gong Y, Ji P, Yang Y, Xie S, Yu T, Xiao Y . Metabolic-Pathway-Based Subtyping of Triple-Negative Breast Cancer Reveals Potential Therapeutic Targets. Cell Metab. 2020; 33(1):51-64.e9. DOI: 10.1016/j.cmet.2020.10.012. View

Herber D, Cao W, Nefedova Y, Novitskiy S, Nagaraj S, Tyurin V . Lipid accumulation and dendritic cell dysfunction in cancer. Nat Med. 2010; 16(8):880-6. PMC: 2917488. DOI: 10.1038/nm.2172. View

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

Lin R, Zhang H, Yuan Y, He Q, Zhou J, Li S . Fatty Acid Oxidation Controls CD8 Tissue-Resident Memory T-cell Survival in Gastric Adenocarcinoma. Cancer Immunol Res. 2020; 8(4):479-492. DOI: 10.1158/2326-6066.CIR-19-0702. View

Sag D, Cekic C, Wu R, Linden J, Hedrick C . The cholesterol transporter ABCG1 links cholesterol homeostasis and tumour immunity. Nat Commun. 2015; 6:6354. PMC: 4347884. DOI: 10.1038/ncomms7354. View

Van den Bossche J, ONeill L, Menon D . Macrophage Immunometabolism: Where Are We (Going)?. Trends Immunol. 2017; 38(6):395-406. DOI: 10.1016/j.it.2017.03.001. View

Mo Y, Wang Y, Xiong F, Ge X, Li Z, Li X . Proteomic Analysis of the Molecular Mechanism of Lovastatin Inhibiting the Growth of Nasopharyngeal Carcinoma Cells. J Cancer. 2019; 10(10):2342-2349. PMC: 6584415. DOI: 10.7150/jca.30454. View

Ugolini A, Tyurin V, Tyurina Y, Tcyganov E, Donthireddy L, Kagan V . Polymorphonuclear myeloid-derived suppressor cells limit antigen cross-presentation by dendritic cells in cancer. JCI Insight. 2020; 5(15). PMC: 7455061. DOI: 10.1172/jci.insight.138581. View

10.

Peng M, Mo Y, Wang Y, Wu P, Zhang Y, Xiong F . Neoantigen vaccine: an emerging tumor immunotherapy. Mol Cancer. 2019; 18(1):128. PMC: 6708248. DOI: 10.1186/s12943-019-1055-6. View

11.

Mayer P, Dinkic C, Jesenofsky R, Klauss M, Schirmacher P, Dapunt U . Changes in the microarchitecture of the pancreatic cancer stroma are linked to neutrophil-dependent reprogramming of stellate cells and reflected by diffusion-weighted magnetic resonance imaging. Theranostics. 2018; 8(1):13-30. PMC: 5743457. DOI: 10.7150/thno.21089. View

12.

Veglia F, Tyurin V, Blasi M, De Leo A, Kossenkov A, Donthireddy L . Fatty acid transport protein 2 reprograms neutrophils in cancer. Nature. 2019; 569(7754):73-78. PMC: 6557120. DOI: 10.1038/s41586-019-1118-2. View

13.

Li X, Wenes M, Romero P, Huang S, Fendt S, Ho P . Navigating metabolic pathways to enhance antitumour immunity and immunotherapy. Nat Rev Clin Oncol. 2019; 16(7):425-441. DOI: 10.1038/s41571-019-0203-7. View

14.

Henrich S, McMahon K, Plebanek M, Calvert A, Feliciano T, Parrish S . Prostate cancer extracellular vesicles mediate intercellular communication with bone marrow cells and promote metastasis in a cholesterol-dependent manner. J Extracell Vesicles. 2021; 10(2):e12042. PMC: 7775568. DOI: 10.1002/jev2.12042. View

15.

Porta C, Consonni F, Morlacchi S, Sangaletti S, Bleve A, Totaro M . Tumor-Derived Prostaglandin E2 Promotes p50 NF-κB-Dependent Differentiation of Monocytic MDSCs. Cancer Res. 2020; 80(13):2874-2888. DOI: 10.1158/0008-5472.CAN-19-2843. View

16.

Paget C, Deng S, Soulard D, Priestman D, Speca S, von Gerichten J . TLR9-mediated dendritic cell activation uncovers mammalian ganglioside species with specific ceramide backbones that activate invariant natural killer T cells. PLoS Biol. 2019; 17(3):e3000169. PMC: 6420026. DOI: 10.1371/journal.pbio.3000169. View

17.

Sirnio P, Vayrynen J, Klintrup K, Makela J, Makinen M, Karttunen T . Decreased serum apolipoprotein A1 levels are associated with poor survival and systemic inflammatory response in colorectal cancer. Sci Rep. 2017; 7(1):5374. PMC: 5511233. DOI: 10.1038/s41598-017-05415-9. View

18.

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

19.

Chapman N, Boothby M, Chi H . Metabolic coordination of T cell quiescence and activation. Nat Rev Immunol. 2019; 20(1):55-70. DOI: 10.1038/s41577-019-0203-y. View

20.

Howie D, Cobbold S, Adams E, Ten Bokum A, Necula A, Zhang W . Foxp3 drives oxidative phosphorylation and protection from lipotoxicity. JCI Insight. 2017; 2(3):e89160. PMC: 5291728. DOI: 10.1172/jci.insight.89160. View