Enhanced lipid biosynthesis in human tumor-induced macrophages contributes to their protumoral characteristics

Rabold, Katrin; Aschenbrenner, Anna C.; Thiele, Christoph; Boahen, Collins K.; Schiltmans, Alexander; Smit, Johannes; Schultze, Joachim L.; Netea, Mihai G.; Adema, Gosse J.; Netea‐Maier, Romana T.

doi:10.1136/jitc-2020-000638

Cited by 33 publications

(34 citation statements)

References 46 publications

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“…While the main mechanism by which TAMs feed tumor cells is angiogenesis, TAMs may engage in similar production and secretion of nutrients. Recently, thyroid carcinoma-and neuroblastoma-induced macrophages were found to upregulate lipid biosynthesis in vitro, supporting their pro-tumoral function including cytokine production [106]. Combined with the finding that macrophages can secrete lipids in vitro and in vivo [107,108], and TAM-derived extracellular vesicles containing lipids [89] this may indicate that not only CAFs and adipocytes but also TAMs "feed" cancer cells.…”

Section: Effect Of Tam Metabolism On Tumor Progressionmentioning

confidence: 88%

Metabolic Cancer-Macrophage Crosstalk in the Tumor Microenvironment

Goede

Driessen

Bossche

2020

Biology

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Tumors consist of a wide variety of cells, including immune cells, that affect tumor progression. Macrophages are abundant innate immune cells in the tumor microenvironment (TME) and are crucial in regulating tumorigenicity. Specific metabolic conditions in the TME can alter the phenotype of tumor-associated macrophages (TAMs) in a direction that supports their pro-tumor functions. One of these conditions is the accumulation of metabolites, also known as oncometabolites. Interactions of oncometabolites with TAMs can promote a pro-tumorigenic phenotype, thereby sustaining cancer cell growth and decreasing the chance of eradication. This review focuses on the metabolic cancer-macrophage crosstalk in the TME. We discuss how cancer cell metabolism and oncometabolites affect macrophage phenotype and function, and conversely how macrophage metabolism can impact tumor progression. Lastly, we propose tumor-secreted exosome-mediated metabolic signaling as a potential factor in tumorigenesis. Insight in these processes may contribute to the development of novel cancer therapies.

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Section: Effect Of Tam Metabolism On Tumor Progressionmentioning

confidence: 88%

Metabolic Cancer-Macrophage Crosstalk in the Tumor Microenvironment

Goede

Driessen

Bossche

2020

Biology

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“…3 b). FASN inhibition significantly suppresses the expressions of TNF-α, IL-6, IL-10, and ROS in TAMs, thereby impairing their pro-tumor activity [ 88 ]. These results suggest that abnormal lipid accumulation is indispensable for TAMs to participate in the pro-tumor immune response.…”

Section: Immunosuppressive Effects Of Lipids In the Tumor Microenvironmentmentioning

confidence: 99%

Contradictory roles of lipid metabolism in immune response within the tumor microenvironment

Lei

et al. 2021

J Hematol Oncol

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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.

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“…40 The inflammatory tumor microenvironment eventually leads to tumor progression and metastasis. [41][42][43] To investigate the role of tumor milieu with FUT7, we analyzed the relationship between FUT7 expression and immune cell infiltration. Growing evidence demonstrated that the infiltration and activation of immune cells were believed to be closely associated with tumor processes, such as breast cancer, 44 lung cancer, 45 uterine corpus endometrial carcinoma, 46 and bladder cancer.…”

Section: Discussionmentioning

confidence: 99%

FUT7 Promotes the Epithelial–Mesenchymal Transition and Immune Infiltration in Bladder Urothelial Carcinoma

Liu¹,

Zheng²,

Chen³

et al. 2021

JIR

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Background Bladder urothelial carcinoma (BLCA) is one of the most frequently appearing, lethal and aggressive malignancies of the genitourinary system with growing morbidity and mortality, which affects human health seriously. Protein glycosylation, catalyzed by specific glycosyltransferase, has been found to be abnormal in several diseases, especially cancer. Fucosyltransferase VII (FUT7), one of the fucosyltransferases, was observed abnormally expressed in various cancers, however, the role of FUT7 in BLCA, and the association between its expression and clinical outcomes or immune infiltration remains unclear. Methodology FUT7 expression in BLCA was analyzed in Oncomine database, which was further confirmed with immunohistochemistry and ELISA. The prognostic value of FUT7 for BLCA was evaluated with PrognoScan database, and its genetic alteration was examined in cBioPortal database. The proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) changes of bladder cancer cells after FUT7 siRNA or cDNA transfection were determined by CCK8, colony formation, transwell and Western blot, respectively. The correlation between FUT7 expression and immune infiltration levels was analyzed in TIMER and TISIDB databases, and the methylation level of FUT7 was detected in UALCAN database. Results The results showed that the expression of FUT7 was increased in BLCA, and patients with high FUT7 level were predicted to have lower overall survival and disease-specific survival rates, which were not influenced by FUT7 genetic alterations. Downregulation FUT7 inhibited the proliferation, migration, invasion and EMT of bladder cancer cells, whereas upregulation of FUT7 showed the opposite effects. We found that FUT7 was positively correlated with immune cell infiltration levels (CD8+ T cells, CD4+T cells, macrophage, neutrophil and dendritic cells), and also the expression of gene markers of immune cells. The negative correlation between FUT7 expression and FUT7 methylation level was observed, among which FUT7 expression was positively correlated with the abundance of 28 kinds of tumor-infiltrating lymphocytes (TILs), while FUT7 methylation level was negatively correlated with TILs. Conclusion Altogether, these findings suggested that FUT7 possessed the potential to serve as a detection biomarker or immunotherapeutic target for BLCA.

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Enhanced lipid biosynthesis in human tumor-induced macrophages contributes to their protumoral characteristics

Cited by 33 publications

References 46 publications

Metabolic Cancer-Macrophage Crosstalk in the Tumor Microenvironment

Metabolic Cancer-Macrophage Crosstalk in the Tumor Microenvironment

Contradictory roles of lipid metabolism in immune response within the tumor microenvironment

FUT7 Promotes the Epithelial–Mesenchymal Transition and Immune Infiltration in Bladder Urothelial Carcinoma

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