Molecular and Cell Biology of Cancer by Rita Fior & Rita Zilhão

Author:Rita Fior & Rita Zilhão
Language: eng
Format: epub
ISBN: 9783030118129
Publisher: Springer International Publishing

6.7 Metabolic Interactions with the Microenvironment

The metabolic state of a cell can have a huge impact on the fate of that particular cell (cell-autonomous) but, more importantly, it can also influence the fate of other cells in its vicinity i.e. have a non-cell-autonomous effect on the tumor microenvironment (TME).

The tumor microenvironment consists of malignant cells, immune cells, non-cancer cell stroma’s, fibroblasts as well as the vasculature and lymphatics of the tumor [76].

As we saw before, in glycolytic tumors, lactate levels of cancer cells are remarkably elevated [77, 78] and are highly correlated with cancer aggressiveness and poor survival [78]. Historically, lactate has been considered as the toxic ‘end of the road’ of aerobic glycolysis, with no major interest. However, recent findings have demonstrated that the accumulation of extracellular lactate has been shown to affect significantly the tumor microenvironment. For instance, increased lactate levels promote the emergence of an immune-permissive microenvironment by attenuating dendritic and T cell activation as well as monocyte migration (◘ Fig. 6.5) [79–81]. Additionally, lactate also promotes the polarization of resident macrophages to an M2 state [82, 83], potentiating an escape from the immune system and favoring proliferation (see ► Chap. 7).

Fig. 6.5Cancer cells alter the chemical composition of the extracellular milieu, which exerts pleiotropic effects on the phenotypes of normal cells that reside in the vicinity of the tumor, as well as the extracellular matrix. Reciprocally, the microenvironment affects the metabolism and signaling responses of cancer cells themselves. (Figure adapted from Pavlova and Thompson [1])

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