Jakub Gołąb

The roles of arginas­es in mit­i­ga­tion of anti­tu­mor immunity

Abstract

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.

Biography/​Link 

https://​immunolo​gia​.wum​.edu​.pl/​e​n​/​n​o​d​e​/​200