Lipid metabolic reprogramming in tumor microenvironment: from mechanisms to therapeutics

Abstract

Lipid metabolic reprogramming is an emerging hallmark of cancer. In order to sustain uncontrolled proliferation and survive in unfavorable environments that lack oxygen and nutrients, tumor cells undergo metabolic transformations to exploit various ways of acquiring lipid and increasing lipid oxidation. In addition, stromal cells and immune cells in the tumor microenvironment also undergo lipid metabolic reprogramming, which further affects tumor functional phenotypes and immune responses. Given that lipid metabolism plays a critical role in supporting cancer progression and remodeling the tumor microenvironment, targeting the lipid metabolism pathway could provide a novel approach to cancer treatment. This review seeks to: (1) clarify the overall landscape and mechanisms of lipid metabolic reprogramming in cancer, (2) summarize the lipid metabolic landscapes within stromal cells and immune cells in the tumor microenvironment, and clarify their roles in tumor progression, and (3) summarize potential therapeutic targets for lipid metabolism, and highlight the potential for combining such approaches with other anti-tumor therapies to provide new therapeutic opportunities for cancer patients.

Progressive sarcopenia and myosteatosis predict prognosis of advanced HCC patients treated with immune checkpoint inhibitors

“…Poorer muscle quality may mediate the immune tolerance of tumor cells to ICIs by affecting T cell function ( 21 ). On the other hand, as the amount of adipose tissue increases, the amount of proinflammatory factors such as leptin, IL-1 and IL-6 increases ( 22 ). Wang et al.…”

Mucosa color and size may indicate malignant transformation of chicken skin mucosa-positive colorectal neoplastic polyps

“…In addition to pits, some features under white light endoscopy can still be used to identify tumors that may have submucosal invasion, such as CSM, which is a plaque or yellow-white speckled mucosal change seen under endoscopy adjacent to colorectal polyps located in the colon or rectum, characterized by fat accumulation in the macrophages of the lamina propria. CSM-positive colorectal polyps are frequently found during routine screening colonoscopies, with a prevalence ranging from 29.5% to 31.3%[ 2 , 4 , 10 ]. According to the related literature[ 2 - 5 , 7 , 10 , 11 ], CSM is involved in a wide range of diseases, including juvenile polyps, neoplastic polyps, advanced colorectal adenoma, submucosal invasion, colorectal cancer, and de novo colorectal cancer.…”

“…Tumor cells are believed to undergo lipid metabolism reprogramming to adapt to the hypoxic, nutrient-poor microenvironment[ 1 ]. Lipid metabolism reprogramming, including lipid uptake, storage, and synthesis, has emerged as a critical feature of cancer[ 2 ] as well as pre-cancerous lesions, such as colorectal adenomas. Colorectal adenomatous mucosal abnormalities identified under standard white light endoscopy are commonly used to detect the early colorectal cancer.…”

Emerging roles of FOXK2 in cancers and metabolic disorders

“…Through regulation of glucose and lipid metabolism, FOXK2 is closely linked to tumor initiation and progression. It is worth noting that tumor cells significantly contribute to remodeling the tumor microenvironment (TME) by producing large amounts of lactate through aerobic glycolysis ( 65 ) and enhancing lipid uptake and oxidation ( 66 ). This TME remodeling, in turn, influences the metabolic profile and immunophenotype of immune cells, leading to their immunosuppression ( 67 ).…”

“…For instance, regulatory T (Treg) cells metabolize lactate to support their proliferative and suppressive functions, and tumor-infiltrating Treg cells require lactate uptake to maintain their heightened suppressive function ( 68 ). Additionally, up-regulation of lipid uptake and FAO elevates lipid metabolism in tumor-associated macrophages (TAMs), Tregs and myeloid-derived suppressor cells (MDSCs), thereby promoting their immunosuppressive function ( 66 ). However, no direct association between FOXK2 and the tumor microenvironment or immune response has been reported thus far; further investigation is warranted.…”