Evaluating programmed death-ligand 1 expression and myeloid-derived suppressor cells as predictive markers in de novo acute myeloid leukemia prognosis

Background
Acute myeloid leukemia (AML) is the most prevalent form of acute leukemia in adults, characterized by rapid disease progression and poor long-term outcomes. Standard chemotherapy achieves short-term remission in many patients; however, long-term remission remains elusive, with fewer than 50% of patients achieving sustained remission. Recent advancements in immunotherapy have brought attention to the potential of targeting immune checkpoints, such as programmed death-ligand 1 (PD-L1), to enhance antitumor immune responses. Additionally, myeloid-derived suppressor cells (MDSCs) are known to expand in cancer and inflammation, where they suppress immune function and contribute to a tumor-permissive environment. Although significant research has been conducted on MDSCs in solid tumours, their specific role in hematological malignancies, including AML, remains underexplored. Understanding PD-L1 expression and MDSCs activity in AML could uncover critical insights for targeted therapies.


Objective
This study aims to assess levels of MDSCs and PD-L1 expression in newly diagnosed AML patients, analyzing their relationship to clinical characteristics, response to induction chemotherapy, and established cytogenetic risk markers. By evaluating these immune parameters, we seek to determine their prognostic value and potential as predictive markers for treatment outcomes in AML patients.


Patients and methods
The study included 50 newly diagnosed AML patients and 50 healthy control individuals selected from the Hematology Departments of Kafrelsheikh University and Zagazig University Hospitals. MDSCs in peripheral blood were quantified through flow cytometry. For PD-L1 expression analysis, total RNA was extracted from blood samples, followed by reverse transcription and real-time PCR quantification. Results were compared with established genetic risk markers, including the presence of Fms-like tyrosine kinase 3 (FLT3), nucleophosmin 1 (NPM1) mutations, and t (8;21), inv (16), and 5q- chromosomal abnormalities, to assess associations with immune marker levels.


Results
Following a 28-day chemotherapy regimen, patients were classified according to response, including complete responders, partial responders, nonresponders, and deceased cases. Nonresponders exhibited significantly elevated median MDSC% and PD-L1 expression levels compared with complete responders, with a strong positive association observed between MDSC% and PD-L1 levels. Receiver operating characteristic analysis demonstrated that MDSC was a more robust predictor of treatment response than PD-L1, with a higher area under the curve. Patients with high PD-L1 levels also showed significantly higher frequencies of 5q- and FLT3 mutations, whereas those with low PD-L1 expression exhibited a higher frequency of NPM1 mutations. For MDSC%, elevated levels correlated significantly with the FLT3 mutation, underscoring a potential association between immune suppression and genetic risk in AML.


Conclusion
The findings of this study highlight the potential of PD-L1 expression and MDSC% as prognostic markers in AML, particularly in predicting response to chemotherapy and in association with high-risk cytogenetic profiles. Given their immune-suppressive roles, targeting PD-L1 and MDSC may provide a therapeutic benefit for AML patients with poor prognostic markers, such as those with FLT3 and 5q- mutations. Anti-PD-L1 therapies, combined with standard chemotherapy or other targeted treatments, could potentially improve outcomes for high-risk AML patients.