Increased lactate in AML blasts upregulates TOX expression, leading to exhaustion of CD8⁺ cytolytic T cells.

ABSTRACT: Recently, the role of lactate as merely an end product of cancer cell metabolism has been reassessed. Lactate has been implicated in more biological processes than previously understood and drives tumor progression. Here, we demonstrated that the bone marrow lactate concentrations in acute myeloid leukemia (AML) patients were substantially higher than those in their healthy control counterparts. Moreover, AML blasts from bone marrow expressed significantly higher lactate dehydrogenase-A (LDHA) levels. Further studies revealed that LDHA expression was regulated through the HIF1α pathway. Elevated lactate levels were indicative of alterations in CD8⁺ T cell cytolytic phenotype and activity. An in vitro study showed that the lactate treatment group had significantly higher percenta

SUBMITTER: Chen Y 

PROVIDER: S-EPMC8640829 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature