The immune checkpoints Cytotoxic T lymphocyte antigen-4 and Lymphocyte activation gene-3 expression is up-regulated in acute myeloid leukemia

Abstract

One of the fundamental hallmarks of cancer is the incapacity of the immune system to eliminate malignancy. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) and lymphocyte activation gene-3 (LAG-3) are considered major inhibitory immune checkpoints expressed on T cells. In this study, we investigated mRNA expression of CTLA-4 and LAG-3, as well as their diagnostic and prognostic value in acute myeloid leukemia (AML) patients. The study involved 60 AML patients and 15 controls. Significantly up-regulated CTLA-4 (P =.005) and LAG-3 (P =.02) mRNA expressions were found in AML patients as compared with the healthy control group. AML patients with unfavorable prognosis also showed significant up-regulation of CTLA-4 (P =.006) and LAG-3 (P =.001) mRNA expressions as compared with those with favorable prognosis. Moreover, multiple stepwise linear regression analysis confirmed that patients prognosis was an independent predictor of both CTLA-4 (P =.003) and LAG-3 (P <.001) expression levels. Receiver-operating characteristic (ROC) curve using combined CTLA-4 and LAG-3 expression showed good diagnostic value for AML (area under the curve [AUC] = 0.80, sensitivity = 80%, specificity = 80% for a cut-off probability >.619) as well as moderate predictive value for unfavorable prognosis (AUC = 0.760, sensitivity = 70%, specificity =100% for a cut-off probability >.617). It is clear from this current study that both CTLA-4 and LAG-3 may be promising prognostic markers in AML patients.