02364nas a2200217   4500008004100000022001400041245011200055210006900167260000900236490000700245520157000252653002801822653003701850653002101887653003001908100001901938700001901957700002001976700002101996856012902017       2024                        eng d  a2054-570300aMetabolic reprogramming and signalling cross-talks in tumour-immune interaction: a system-level exploration0 aMetabolic reprogramming and signalling crosstalks in tumourimmun  cMAR 0 v113 a<p>
	Tumour-immune microenvironment (TIME) is pivotal in tumour progression and immunoediting. Within TIME, immune cells undergo metabolic adjustments impacting nutrient supply and the anti-tumour immune response. Metabolic reprogramming emerges as a promising approach to revert the immune response towards a pro-inflammatory state and conquer tumour dominance. This study proposes immunomodulatory mechanisms based on metabolic reprogramming and employs the regulatory flux balance analysis modelling approach, which integrates signalling, metabolism and regulatory processes. For the first time, a comprehensive system-level model is constructed to capture signalling and metabolic cross-talks during tumour-immune interaction and regulatory constraints are incorporated by considering the time lag between them. The model analysis identifies novel features to enhance the immune response while suppressing tumour activity. Particularly, altering the exchange of succinate and oxaloacetate between glioma and macrophage enhances the pro-inflammatory response of immune cells. Inhibition of glutamate uptake in T-cells disrupts the antioxidant mechanism of glioma and reprograms metabolism. Metabolic reprogramming through adenosine monophosphate (AMP)-activated protein kinase (AMPK), coupled with glutamate uptake inhibition, was identified as the most impactful combination to restore T-cell function. A comprehensive understanding of metabolism and gene regulation represents a favourable approach to promote immune cell recovery from tumour dominance.</p>
10ametabolic reprogramming10asignalling-metabolic cross-talks10asystem modelling10atumour-immune interaction1 aShukla, Mudita1 aBhowmick, Rupa1 aGanguli, Piyali1 aSarkar, Ram, Rup  uhttps://library.ncl.res.in/content/metabolic-reprogramming-and-signalling-cross-talks-tumour-immune-interaction-system-level