The progression of acute myeloid leukemia(AML)—the most severe blood/bone marrow cancer—is determined by the ability of malignant cells to escape host immune surveillance.However,the systemic regulatory mechanisms u...The progression of acute myeloid leukemia(AML)—the most severe blood/bone marrow cancer—is determined by the ability of malignant cells to escape host immune surveillance.However,the systemic regulatory mechanisms underlying this phenomenon remain largely unknown.In this study,we discovered a fundamental systemic biochemical strategy that allows AML cells to employ physiological systems within the body to survive and escape immune attack.We found that AML cells use a crucial human adrenal cortex hormone(cortisol)to induce the expression of neuronal receptor latrophilin 1(LPHN1),which facilitates exocytosis.This receptor interacts with the blood plasma protein fibronectin leucine rich transmembrane protein 3(FLRT3)to cause secretion of the immune suppressor galectin-9,which impairs the anticancer activities of cytotoxic lymphoid cells.展开更多
基金This work was supported by a Daphne Jackson Trust postdoctoral fellowship(to I.M.Y.)the University of Kent Faculty of Sciences Research Fund(to V.S.).We thank Diamond Light Source for access to B23 beamline(SM12578).
文摘The progression of acute myeloid leukemia(AML)—the most severe blood/bone marrow cancer—is determined by the ability of malignant cells to escape host immune surveillance.However,the systemic regulatory mechanisms underlying this phenomenon remain largely unknown.In this study,we discovered a fundamental systemic biochemical strategy that allows AML cells to employ physiological systems within the body to survive and escape immune attack.We found that AML cells use a crucial human adrenal cortex hormone(cortisol)to induce the expression of neuronal receptor latrophilin 1(LPHN1),which facilitates exocytosis.This receptor interacts with the blood plasma protein fibronectin leucine rich transmembrane protein 3(FLRT3)to cause secretion of the immune suppressor galectin-9,which impairs the anticancer activities of cytotoxic lymphoid cells.
