3103 – OPTIMAL COMBINATION OF IMMUNE CHECKPOINTS PREDICTS ADVERSE OUTCOMES IN PATIENTS WITH ACUTE MYELOID LEUKEMIA

Abstract

<h3>Background</h3> Immunotherapy with immune checkpoint inhibitors (ICIs) for solid tumors had significantly improved overall survival. This type of therapy has not been evaluated well in acute myeloid leukemia (AML), and basic information on immune checkpoint (IC) expression levels for comprehensively evaluating the prognosis of patients with AML is lacking. <h3>Methods</h3> The prognostic value of ICs in AML patients was explored by using RNA-seq and mutant data of 176 AML patients from the Cancer Genome Atlas (TCGA) database and further validated the finding using bone marrow (BM) samples from 62 patients with de novo AML from our department by quantitative real-time PCR. <h3>Results</h3> Both TCGA data and validation results indicated that high expression of PD-1, PD-L1, and PD-L2 was associated with poor overall survival (OS) in AML patients. In addition, increased co-expression of PD-1 and CTLA-4 (3-year OS: 30% vs 0% (TGCA data), 57% vs 31% (validation group), respectively) or PD-L2 and CTLA-4 (3-year OS: 20% vs 0% (TGCA data), 57% vs 33% (validation group), respectively) correlated with poor AML OS (P < 0.05). Moreover, co-expression of PD-1/PD-L1, PD-1/PD-L1/PD-L2, and PD-1/LAG-3 correlated with poor OS in AML patients with FLT3mut, RUNX1mut, and TET2mut, respectively (P < 0.05). <h3>Conclusions</h3> High expression of ICs in the BM leukemia cells of AML patients correlated with poor OS. Co-expressions of PD-1/CTLA-4, PD-L2/CTLA-4, PD-1/PD-L1, PD-1/PD-L1/PD-L2, and PD-1/LAG-3 might be used as novel immune predictors for patient OS in AML, and might guide the best choice for precision immune checkpoint blockade in the future.