Targeting lipid metabolism reprogramming of immunocytes in response to the tumor microenvironment stressor: A potential approach for tumor therapy

Abstract

The tumor microenvironment (TME) has become a major research focus in recent years. The TME differs from the normal extracellular environment in parameters such as nutrient supply, pH value, oxygen content, and metabolite abundance. Such changes may promote the initiation, growth, invasion, and metastasis of tumor cells, in addition to causing the malfunction of tumor-infiltrating immunocytes. As the neoplasm develops and nutrients become scarce, tumor cells transform their metabolic patterns by reprogramming glucose, lipid, and amino acid metabolism in response to various environmental stressors. Research on carcinoma metabolism reprogramming suggests that like tumor cells, immunocytes also switch their metabolic pathways, named “immunometabolism”, a phenomenon that has drawn increasing attention in the academic community. In this review, we focus on the recent progress in the study of lipid metabolism reprogramming in immunocytes within the TME and highlight the potential target molecules, pathways, and genes implicated. In addition, we discuss hypoxia, one of the vital altered components of the TME that partially contribute to the initiation of abnormal lipid metabolism in immune cells. Finally, we present the current immunotherapies that orchestrate a potent antitumor immune response by mediating the lipid metabolism of immunocytes, highlight the lipid metabolism reprogramming capacity of various immunocytes in the TME, and propose promising new strategies for use in cancer therapy.

Fatty acid metabolism is related to the immune microenvironment changes of gastric cancer and RGS2 is a new tumor biomarker

“…Recently, increasing attention has been paid to the role of membrane fatty acids (with respect to e.g. the ratio of saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids) in promoting cell survival, limiting lipotoxicity, and iron-dependent cell death ( 19 – 21 ). Here, eight fatty acid metabolism-related genes related to gastric cancer prognosis were identified based on an analysis of genomic information of 373 STAD samples and 32 paracancerous tissue samples using univariate COX regression, clustering, and principal component analyses.…”

ALDOB represents a potential prognostic biomarker for patients with clear cell renal cell carcinoma

“…Metabolic patterns of cellular processes have been reported to be associated with a variety of tumorigenesis ( 31 ). Recent developments in the field of cancers have led to an interest in the changes in the metabolic pathways that control tumor energy and biosynthesis, known as metabolic reprogramming, which was considered to be a core hallmark of cancer ( 32 , 33 ).…”

Orchestral role of lipid metabolic reprogramming in T-cell malignancy

“…Impairment of macrophages’ antitumor activity and promotion of growth by tumor-associated macrophages are well established in the lymphoma of T-cell origin ( 174 , 175 ). The inhibition of SREBP makes leukemia cells susceptible to anti-PD-1 immunotherapy ( 176 ). Moreover, inhibition of SREBP1 negatively affects the tumor growth-promoting ability of tumor-associated macrophages ( 173 ).…”