Lipid metabolism associated crosstalk: the bidirectional interaction between cancer cells and immune/stromal cells within the tumor microenvironment for prognostic insight

Abstract

Cancer is closely related to lipid metabolism, with the tumor microenvironment (TME) containing numerous lipid metabolic interactions. Cancer cells can bidirectionally interact with immune and stromal cells, the major components of the TME. This interaction is primarily mediated by fatty acids (FAs), cholesterol, and phospholipids. These interactions can lead to various physiological changes, including immune suppression, cancer cell proliferation, dissemination, and anti-apoptotic effects on cancer cells. The physiological modulation resulting from this lipid metabolism-associated crosstalk between cancer cells and immune/stromal cells provides valuable insights into cancer prognosis. A comprehensive literature review was conducted to examine the function of the bidirectional lipid metabolism interactions between cancer cells and immune/stromal cells within the TME, particularly how these interactions influence cancer prognosis. A novel autophagy-extracellular vesicle (EV) pathway has been proposed as a mediator of lipid metabolism interactions between cancer cells and immune cells/stromal cells, impacting cancer prognosis. As a result, different forms of lipid metabolism interactions have been described as being linked to cancer prognosis, including those mediated by the autophagy-EV pathway. In conclusion, understanding the bidirectional lipid metabolism interactions between cancer cells and stromal/immune cells in the TME can help develop more advanced prognostic approaches for cancer patients.

Fig. 1

Diagrammatic presentation of the lipid mediated interaction between cancer cells and cellular components of the TME. Cancer cells can influence the lipid composition of the TME and therefore influence stromal and immune cells. Simultaneously, stromal and immune cells can also affect cancer cells using those lipid metabolites, further affecting cancer prognosis

Fig. 2

Simplified diagrammatic presentation that shows the biogenesis of exosomes. Multivesicular bodies responsible for the secretion of exosomes into the extracellular environment can also fuse with autophagosomes, which can fuse with lysosomes to be degraded, also known as autophagy. The fusion between autophagosomes and multivesicular bodies generates amphisomes, which can also secret exosomes into the TME

Fig. 3

Simplified diagrammatic presentation that shows the novel autophagy-EV pathway. The lipid in the EVs secreted from the autophagy-EV pathway can mediated the interaction between cancer cells with immune/stromal cells in the TME and possibly trigger autophagy processes in these cells and affect cancer prognosis

Fig. 4

Lipid-metabolism associated interaction between cancer cells and adipocytes. Cancer cells and adipocytes have shown to interfere with each other via EVs, free FAs, and cholesterol as indicated in the diagram. Phospholipid have played an indirect part, which is not presented on the diagram. Notably, adipocytes can be modified into CAFs, further complexing its role in the TME

Fig. 5

EBV-associated lipid metabolic interaction between B-cells and cancer cells. EBV can invade both B-cells and cancer cells, presented by the existence of LMP1 on these cells’ membrane. In cancer cells invaded by EBV, LMP1 from either cancer cell membrane or B-cell membrane can trigger activated lipid metabolism in cancer cells. When cancer cells are not invaded by EBV, the B-cells invaded by EBV with LMP1 can also trigger increased level of lipid metabolism in cancer cells. The lipid metabolism can be featured by a closed loop between SREBP1, FASN, and LD

Fig. 6

HBV-associated B-cell cancer cell EV-autophagy pathway. HBV can infect some liver cells, which can release EVs before they are transformed into cancer cells. The bcl-2 and lamp2a in the EVs can strengthen the anti-apoptotic effect of B-cells and increase the level of free FAs in liver cancer cells

Fig. 7

Macrophage cancer cell EV-autophagy pathway. Macrophages can release EVs into cancer cells releasing miR-4535. Cancer cells can release EVs into macrophages and induce autophagy and M2-like macrophage polarization