TIGIT-associated immune cell exhaustion in pediatric B-cell acute lymphoblastic leukemia: An integrated clinical and...

Immune checkpoint dysregulation contributes to cytotoxic lymphocyte exhaustion in hematologic malignancies. TIGIT, an inhibitory immune receptor expressed on activated T and natural killer (NK) cells, is a key regulator of immune exhaustion. However, its transcriptional landscape in pediatric acute lymphoblastic leukemia (ALL) remains unclear. TIGIT expression was investigated using institutional clinical samples, TARGET-ALL bulk RNA sequencing, and single-cell RNA sequencing data (GSE154109). TIGIT expression was significantly elevated in pediatric B-ALL compared with healthy controls (p = 0.0141), with preliminary discriminatory capacity (AUC = 0.875) in this exploratory cohort. Exploratory subgroup analyses suggested higher TIGIT expression in some clinical subgroups. Subgroup findings were interpreted conservatively in view of the limited sample sizes. Bulk transcriptomic analysis of 1587 TARGET-ALL samples detected TIGIT in 10%, suggesting a distinct subset. Single-cell transcriptomics revealed TIGIT expression in CD8⁺ T cells and NK cells. Pathway analysis showed suppression of antigen presentation and interferon signaling, while cytotoxic cells exhibited transcriptional features consistent with exhaustion. Together, these findings provide preliminary evidence linking TIGIT expression to immune exhaustion-related transcriptional signatures in pediatric B-ALL. This interpretation is based on transcriptomic evidence and remains provisional pending protein-level and functional validation.