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.