Lipid metabolic reprogramming in colorectal cancer: Insights to mechanisms and therapeutics

Table 1 Lipid metabolism in immune cells

Immune cells	Key metabolic alteration	Mechanisms	Effect on immune cells	Ref.
CD8 + T cells	CPT1 (increase)	Enhanced FAO via PPAR signaling activation	Enhanced antitumor function	Chowdhury et al[136]
	CD36 (increase)	CD36-mediated OxLDL uptake (increase)-lipid peroxidation-p38 activation	Impairing anti-tumor immune responses	Xu et al[13]
Treg cells	CD36 (increase)	Upregulated CD36 activates PPAR-β mitochondrial fitness	Enhanced immunosuppression	Wang et al[11]
	FAS (increase)	SREBP/FASN axis drives lipid synthesis, inhibiting SREBP exhibits a rapid clearance of tumor cells	Enhanced immunosuppression	Lim et al[143]
	Cholesterl synthesis (increase)	mTORC1 signaling cholesterol synthesis (increase)	Enhanced immunosuppression	Zeng et al[144]
TAMs	CD36 (increase)	Lipid uptake (increase)	M2 polarization, suppression of CD8 + T cell function	Yang et al[145]
	FAS (increase)	SREBP1-driven fatty acid synthesis (increase)	Orchestrate tumor-associated immunosuppression	Liu et al[146]
	LD (increase)		Tumor growth enhancement, inhibiting LD leads to tumor growth impairment	Wu et al[147]
DCs	Scavenger receptor A (increase)	Lipids uptake (increase)	Impaired antigen presentation	Herber et al[148]
	OxLDL	CD36/TLR2/TLR6 complex internalizes OxLDL-activate NF-κB/NLRP3/cGAS-STING	Enhance anti-tumor immunity	Ma et al[149]
	FFAR2	FFAR2 Loss-IL-27 (increase)-CD8 + T cell exhaustion	Prevent colorectal carcinogenesis	Lavoie et al[150]
NK cells	Obesity	PPAR-α/δ induced by obesity suppresses mTOR glycolysis-IFN-γ (decrease)	Impaired cytotoxicity	Michelet et al[151]
	MSR1, CD36 and CD68	Lipid accumulation	NK cell dysfunction	Niavarani et al[152]
MDSCs	FATP2 (increase)	FATP2 mediates AA uptake PGE2 synthesis	Enhanced immunosuppression	Veglia et al[153]
	XBP1 (increase)	XBP1 drives sEV-cholesterol release immunosuppression		Yang et al[154]
CAFs	FASN (increase)	CAFs secretes lipids absorbed by CRC cells EMT (increase)	Promotion of tumor migration	Gong et al[155]
	CPT1A (increase)	CPT1A (increase) enhances FAO energy supply	Promotion of peritoneal metastasis	Peng et al[87]
	12(S)-hydroxy eicosatetraenoic acid	Induces the retraction of cancer-associated fibroblasts via MLC2, RHO/ROCK and Ca2+ signaling	Enforced invasiveness of CRC	Stadler et al[156]

CD: Cluster of differentiation; Treg: Regulatory T cell; FAS: Fatty acid synthesis; TAM: Tumor-associated macrophages; DCs: Dendritic cells; CPT: Carnitine palmitoyl transferase; FASN: Fatty acid synthase; SREBP: Sterol regulatory element-binding protein; LD: Lipid droplet; OxLDL: Oxidized low-density lipoproteins; FFAR2: Free fatty acid receptor 2; FAO: Fatty acid oxidation; PPAR: Peroxisome proliferator-activated receptor; mTORC1: Mammalian target of rapamycin complex 1; TLR: Toll-like receptor; NF-κB: Nuclear factor kappa-B; cGAS/STING: Cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes signaling; IL: Interleukin; NK: Natural killer; MDSCs: Myeloid-derived suppressor cells; CAF: Cancer-associated fibroblast; FATP2: Fatty acid transport protein 2; XBP1: X-box binding protein 1; IFN: Interferon; AA: Arachidonic acid; PGE2: Prostaglandin E2; sEV: Small extracellular vesicle; CRC: Colorectal cancer; EMT: Epithelial-mesenchymal transition; MLC2: Myosin light chain 2; Ca²⁺: Calcium ion.