CD244 modulates bone marrow infiltrating CD8+ T cells and serves as a prognostic and immunotherapeutic target in acute myeloid leukemia.

BACKGROUND

The Signaling Lymphocyte Activation Molecule (SLAM) receptor family regulates immune homeostasis across diverse immune cells. This study investigates the immunomodulatory role of CD244 in CD8+T cells within the acute myeloid leukemia (AML) bone marrow microenvironment.

METHODS

Using pan-cancer analysis, Gene Expression Omnibus (GEO) datasets, functional experiments, and orthotopic AML mouse models, we systematically evaluated CD244 expression and its correlations with gene mutations, clinical prognosis, and immune microenvironment profiles in AML.

RESULTS

Pan-cancer analysis revealed high CD244 expression in AML, associated with poor prognosis. GSE6891 data showed biallelic CEBPA mutations upregulated CD244, while NPM1 mutations had lower expression. TCGA-LAML analysis linked CD244 to immune cell infiltration. Flow cytometry validated elevated CD244 on bone marrow-infiltrating CD8+T cells, predominantly on terminally differentiated effector memory T subsets in AML patients, with impaired cytokine secretion compared to healthy controls. Orthotopic AML mouse models also confirmed enhanced CD244 expression in CD62Llow/highCD44high CD8+T cell subsets. Additionally, CD244 correlated positively with CD161/CD57 and negatively with CD27. And anti-CD244 antibody could significantly enhance T-cell-mediated anti-AML efficacy in cytotoxicity assays.

CONCLUSIONS

CD244 drives immunomodulation via dysregulated CD8+T cell differentiation and cytokine secretion, positioning it as a prognostic biomarker and a promising target for immunotherapy in AML.