Jakub Gołąb
Abstract
The roles of arginases in mitigation of antitumor immunity
Immunotherapy has demonstrated significant activity in a broad range of cancer types, but still the majority of patients receiving it do not maintain durable therapeutic responses. Amino acid metabolism is a critical regulator of the immune response, and its modulating becomes a promising approach in various forms of immunotherapy. Insufficient concentrations of essential amino acids restrict T-cells activation and proliferation.
However, only arginases, that degrade ʟ-arginine, as well as enzymes that hydrolyze ʟ-tryptophan are substantially increased in cancer. Nearly all types of myeloid cells were reported to produce arginases and the increased numbers of various populations of myeloid-derived suppressor cells and macrophages correlate with inferior clinical outcomes of cancer patients.
We investigated the role of arginases in the modulation of antitumor immune response in various tumor models. The presentation will address the role of arginases produced by myeloid cells in regulating various populations of immune cells, discuss molecular mechanisms of immunoregulatory processes involving ʟ-arginine metabolism and outline therapeutic approaches to mitigate the negative effects of arginases on antitumor immune response.
Development of potent arginase inhibitors, with improved pharmacokinetic properties, may lead to the elaboration of novel therapeutic strategies based on targeting immunoregulatory pathways controlled by ʟ-arginine degradation.