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Stearoyl-CoA Desaturase in CD4 T Cells Suppresses Tumor Growth Through Activation of the CXCR3/CXCL11 Axis in CD8 T Cells

Overview
Journal Cell Biosci
Publisher Biomed Central
Specialty Biology
Date 2024 Nov 15
PMID 39543650
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Abstract

Background: Within the tumor microenvironment, altered lipid metabolism promotes cancer cell malignancy by activating oncogenic cascades; however, impact of lipid metabolism in CD4 tumor-infiltrating lymphocytes (TILs) remains poorly understood. Here, we elucidated that role of stearoyl-CoA desaturase (SCD) increased by treatment with cancer-associated fibroblast (CAF) supernatant in CD4 T cells on their subset differentiation and activity of CD8 T cells.

Results: In our study, we observed that CD4 TILs had higher lipid droplet content than CD4 splenic T cells. In tumor tissue, CAF-derived supernatant provided fatty acids to CD4 TILs, which increased the expression of SCD and oleic acid (OA) content. Increased SCD expression by OA treatment enhanced the levels of Th1 cell markers TBX21, interleukin-2, and interferon-γ. However, SCD inhibition upregulated the expression of regulatory T (Treg) cell markers, FOXP3 and transforming growth factor-β. Comparative fatty acid analysis of genetically engineered Jurkat cells revealed that OA level was significantly higher in SCD-overexpressing cells. Overexpression of SCD increased expression of Th1 cell markers, while treatment with OA enhanced the transcriptional level of TBX21 in Jurkat cells. In contrast, palmitic acid which is higher in SCD-KO cells than other subclones enhanced the expression of Treg cell markers through upregulation of mitochondrial superoxide. Furthermore, SCD increased the secretion of the C-X-C motif chemokine ligand 11 (CXCL11) from CD4 T cells. The binding of CXCL11 to CXCR3 on CD8 T cells augmented their cytotoxic activity. In a mouse tumor model, the suppressive effect of CD8 T cells on tumor growth was dependent on CXCR3 expression.

Conclusion: These findings illustrate that SCD not only orchestrates the differentiation of T helper cells, but also promotes the antitumor activity of CD8 T cells, suggesting its function in adverse tumor microenvironments.

References
1.
Gorjao R, Cury-Boaventura M, de Lima T, Curi R . Regulation of human lymphocyte proliferation by fatty acids. Cell Biochem Funct. 2007; 25(3):305-15. DOI: 10.1002/cbf.1388. View

2.
Nicholas D, Zhang K, Hung C, Glasgow S, Aruni A, Unternaehrer J . Palmitic acid is a toll-like receptor 4 ligand that induces human dendritic cell secretion of IL-1β. PLoS One. 2017; 12(5):e0176793. PMC: 5413048. DOI: 10.1371/journal.pone.0176793. View

3.
Li J, Ge M, Lu S, Shi J, Li X, Wang M . Pro-inflammatory effects of the Th1 chemokine CXCL10 in acquired aplastic anaemia. Cytokine. 2017; 94:45-51. DOI: 10.1016/j.cyto.2017.04.010. View

4.
Zhang J, Xu X, Zhu H, Wang Y, Hou Y, Liu Y . Dietary fish oil supplementation alters liver gene expressions to protect against LPS-induced liver injury in weanling piglets. Innate Immun. 2019; 25(1):60-72. PMC: 6830890. DOI: 10.1177/1753425918821420. View

5.
Dalla Valle A, Vertongen P, Spruyt D, Lechanteur J, Suain V, Gaspard N . Induction of Stearoyl-CoA 9-Desaturase 1 Protects Human Mesenchymal Stromal Cells Against Palmitic Acid-Induced Lipotoxicity and Inflammation. Front Endocrinol (Lausanne). 2019; 10:726. PMC: 6822410. DOI: 10.3389/fendo.2019.00726. View