VISTA is a potential target for immunotherapy in B-cell acute lymphoblastic leukemia in children

Abstract

Abstract Immune checkpoints expressed by immune cells are critical mediators of immune suppression in cancer. Recently, the role of VISTA, an immune checkpoint, in suppressing T cells has been highlighted in several studies. However, its involvement in B-cell acute lymphoblastic leukemia (B-ALL) remains underexplored. In this study, we analyzed the expression of VISTA, the immune-regulatory marker CD244, and its corresponding ligand CD48. Additionally, we examined the expression of the transcription factors FOXD3 and PVRL2 in pediatric patients with B-ALL. Peripheral blood samples from pediatric patients with naïve B-ALL were analyzed using flow cytometry. Additionally, real-time PCR was used to evaluate the downstream regulatory gene FOXD3 expression and the immune regulator PVRL2. VISTA was overexpressed on blasts in B-ALL patients. Also, the frequency of CD3+CD8+VISTA+ T cytotoxic cells was significantly higher in patients compared to controls, while CD3+CD4+VISTA+ T helper cells were reduced. CD19+VISTA+ cells were more abundant in the complete remission group compared to the non-complete remission group. FOXD3, a key regulator of VISTA, was significantly downregulated in B-ALL, consistent with VISTA overexpression. The CD244/CD48 interaction, which can promote anti-tumoral immune responses, showed a reduction in CD3+CD4+CD48+ and CD19+CD48+ cells, while CD3+CD8+CD48+ cells were increased. VISTA overexpression and FOXD3 downregulation in B-ALL, alongside altered CD48, and PVRL2 expression, highlight mechanisms of immune evasion. These findings position VISTA as a promising biomarker and target for B-ALL immunotherapy.