Ionic modulation of immune checkpoint proteins

TY - CONF

T1 - Ionic modulation of immune checkpoint proteins

AU - Shandell, Mia Ann

AU - Lawrence, Samantha

AU - Brackenbury, Will

AU - Lagos, Dimitris

PY - 2019/6/19

Y1 - 2019/6/19

N2 - Despite extensive basic and clinical research on immune checkpoint regulatory pathways, little is known about the effects of the ionic tumour microenvironment on immune checkpoint expression and function. We screened effects of ion channel modulating compounds on indoleamine-2',3'-dioxygenase (IDO1) activity. Here, we describe a mechanistic link between Na+/K+ ATPase inhibition by cardiac glycosides and activity of IDO1, a well-characterized immune checkpoint. IDO1 catalyses the rate-limitig step of tryptophan catabolim and inhibits the immune response to the tumour by local depletion of tryptophan, an amino acid essential for anabolic functions in cancer and T cells.

AB - Despite extensive basic and clinical research on immune checkpoint regulatory pathways, little is known about the effects of the ionic tumour microenvironment on immune checkpoint expression and function. We screened effects of ion channel modulating compounds on indoleamine-2',3'-dioxygenase (IDO1) activity. Here, we describe a mechanistic link between Na+/K+ ATPase inhibition by cardiac glycosides and activity of IDO1, a well-characterized immune checkpoint. IDO1 catalyses the rate-limitig step of tryptophan catabolim and inhibits the immune response to the tumour by local depletion of tryptophan, an amino acid essential for anabolic functions in cancer and T cells.

M3 - Other

SP - Proc Physiol Soc 43, C044

T2 - Physiology 2019

Y2 - 7 July 2019 through 10 July 2019

ER -