Fig. 3

Lipid metabolism in pro-tumor immune responses. a FAs taken in via CD36 or FATPs mediate the immunosuppressive response via eliciting Teffs exhaustion or stimulating PPAR-β and FAO in Tregs. FoxP3 also works as a critical immunosuppressive mediator by regulating FAs metabolism in Tregs. Cholesterol induces the expression of PD-1 and 2B-4 and subsequent exhaustion of Teffs to promote tumor growth. Leptin in the TME suppresses Teffs through the PD-1-STAT3-CPT1B pathway to enhance FAO and eliminate cytotoxicity. b FAs taken in via transporter proteins or de novo synthesis in macrophages can stimulate CPT1B and FAO, thus enhancing the secretion of immunosuppressive cytokines like ARG-1 and IL-10 or suppressing inflammatory cytokines like TNF-α, IL-6, and IL-1β. M-CSF from the TME enhances FASN expression. Macrophages with high expression of ABCG1 transport cholesterol outside and promote IL-4 expression and tumor progression. c MSR1 and TGFBR1 facilitate FAs transportation and LD formation in DCs, which influence antigen processing, TLR stimulation, and proliferation of DCs. d PUSFAs taken in by CD36 on MDSCs activate STAT3/5 and stimulate ROS production. M-CSF promotes FASN and FA production in MDSCs, which subsequently enhance immunosuppressive cytokine production, like IL-10, ARG-1, and iNOS. e FAs suppress the cytotoxicity of NK cells through the mTOR-PPAR signaling pathway. f LDs are enriched in tumor-infiltrating neutrophils due to elevated exogenous intake of FAs and downregulation of lipolysis enzyme ATGL caused by PGE2. LDs of neutrophils are then transported to tumor cells to facilitate their proliferation and progression. Oxysterol promotes the migration of neutrophils via binding to CXCR2