Orchestral role of lipid metabolic reprogramming in T-cell malignancy

Abstract

The immune function of normal T cells partially depends on the maneuvering of lipid metabolism through various stages and subsets. Interestingly, T-cell malignancies also reprogram their lipid metabolism to fulfill bioenergetic demand for rapid division. The rewiring of lipid metabolism in T-cell malignancies not only provides survival benefits but also contributes to their stemness, invasion, metastasis, and angiogenesis. Owing to distinctive lipid metabolic programming in T-cell cancer, quantitative, qualitative, and spatial enrichment of specific lipid molecules occur. The formation of lipid rafts rich in cholesterol confers physical strength and sustains survival signals. The accumulation of lipids through de novo synthesis and uptake of free lipids contribute to the bioenergetic reserve required for robust demand during migration and metastasis. Lipid storage in cells leads to the formation of specialized structures known as lipid droplets. The inimitable changes in fatty acid synthesis (FAS) and fatty acid oxidation (FAO) are in dynamic balance in T-cell malignancies. FAO fuels the molecular pumps causing chemoresistance, while FAS offers structural and signaling lipids for rapid division. Lipid metabolism in T-cell cancer provides molecules having immunosuppressive abilities. Moreover, the distinctive composition of membrane lipids has implications for immune evasion by malignant cells of T-cell origin. Lipid droplets and lipid rafts are contributors to maintaining hallmarks of cancer in malignancies of T cells. In preclinical settings, molecular targeting of lipid metabolism in T-cell cancer potentiates the antitumor immunity and chemotherapeutic response. Thus, the direct and adjunct benefit of lipid metabolic targeting is expected to improve the clinical management of T-cell malignancies.

Glycerol‐3‐phosphate acyltransferase 3‐mediated lipid droplets accumulation confers chemoresistance of colorectal cancer

“…Similar results were also found in other reports. 13,29 Lipid metabolic reprogramming regulated CD8+ T-cell activity in tumor aggressiveness via inhibiting ICD.…”

Melatonin: a modulator in metabolic rewiring in T-cell malignancies

“…Metabolic rewiring is a powerful strategy employed by malignant cells to adapt to different environmental conditions and physiological demands. Through metabolic rewiring, the metabolic pathways are modified and preferences, ultimately influencing crucial cellular functions such as energy production, signaling mechanism, biosynthesis, and survival ( 117 ). Metabolic reprogramming has been implicated in cancer progression ( 118 ).…”

“…FASN is an enzyme that catalyzes fatty acid synthesis through acetyl-CoA. Fatty acids are utilized by mitochondria to generate ATP ( 117 ) ( Figure 5 ).…”

Gene Expression, Morphology, and Electrophysiology During the Dynamic Development of Human Induced Pluripotent Stem Cell-Derived Atrial- and Ventricular-Like Cardiomyocytes [Letter]

“… 4 Additionally, the dynamic shift in mitochondrial abundance and lipid droplet content suggests a metabolic reprogramming that aligns with functional development. 5 While the study effectively demonstrates dynamic changes in gene expression and morphology, a deeper exploration of the electrophysiological maturation is warranted. Although resting and action potential amplitudes remained similar, the observed prolongation of action potential duration during development requires further investigation.…”