SLC43A2-mediated immune cell infiltration: a potential therapeutic target in acute myeloid leukemia

Tumor cells compete with T cells for methionine by overexpressing SLC43A2 (solute carrier family 43 member 2), leading to T cell exhaustion. However, the correlation between SLC43A2 and immune infiltration or malignant features in acute myeloid leukemia (AML) has rarely been explored.

We obtained gene expression data and clinical information from 173 AML patients in The Cancer Genome Atlas (TCGA) database. Statistical analyses were performed using R (v4.0.5). Differential expression, immune infiltration, functional enrichment, and survival analyses were conducted using online databases, including GEPIA, GSCA Lite, Kaplan-Meier Plotter, KEGG, and TIMER2. In vitro, we established SLC43A2-knockdown cell lines and validated SLC43A2 expression via PCR. Flow cytometry was employed to analyze cell viability, counts, apoptotic cell ratios, and immune cell infiltration.

SLC43A2 was highly expressed in AML and associated with poorer survival. Enrichment analysis revealed that SLC43A2 is involved in lymphocyte activation, leukocyte adhesion, and immune response regulatory signaling pathways. Immune infiltration results showed that SLC43A2 positively correlated with immune exhaustion markers (all p < 0.05) and negatively correlated with CD8+ T, NK, and B cell infiltration (all p < 0.05). We constructed an SPI1-hsa-miR-31-5p-SLC43A2 transcriptional network to support the role of SLC43A2. In vitro experiments have shown that SLC43A2 is negatively correlated with the infiltration level of immune cells and positively correlated with the expression levels of PDCD1 and CTLA4. Moreover, lower SLC43A2 expression was associated with enhanced T cell cytotoxicity.

The SLC43A2 gene may serve as a diagnostic, prognostic, and potential immune-related biomarker for AML patients. Blocking SLC43A2-associated signaling pathways could provide novel insights into immunotherapy for AML.