Research progress in regulation of tumor immunity by glutamine metabolism inhibitors
Glutamine(Gin)is the key carbon and nitrogen donor and energy source of the body.It is not only a critical player in tumorigenesis but also involved in regulating the development and activation of immune cells.Rapidly proliferating tumor cells will obtain a large amount of nutrients from the tumor microenvironment,leading to depletion of Gin,which significantly inhibits the activity and function of T cells and induces T cell exhaustion.The proliferation of tumor cells was suppressed by Gln metabolism inhibitors,including Gln mimetics,glutaminase inhibitors,and Gln transporter inhibitors.Meanwhile,T cell depletion was not further aggravated.Instead,the tumor microenvironment was improved to enhance the antitumor immune response by regulating multiple mechanisms such as immune checkpoint molecule expression,extracellular matrix structure remodeling,and tumor-associated macrophage polarization.Combining Gln metabolic inhibitors with immune checkpoint inhibitors can also exert synergistic effects.
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