A recent study published in The Journal of Clinical Investigation has shed light on a potential breakthrough in the treatment of acute myeloid leukemia (AML). While immune checkpoint inhibitors targeting the PD-1 molecule on T-cells have shown efficacy in various cancers, they have proven ineffective in AML. However, researchers have identified a related molecule, PD-1H or VISTA, as a promising therapeutic target for AML.

Led by Tae Kon Kim, MD, PhD, an assistant professor of Medicine and Pathology, Microbiology, and Immunology at Vanderbilt University Medical Center, the study explored the role of VISTA in AML progression. The research revealed that VISTA, though structurally similar to PD-1, operates differently, primarily by promoting the growth of AML cells and evading T-cell immune responses.

Through experiments utilizing mouse models and analysis of patient data, the researchers demonstrated that blocking VISTA molecules on T-cells either through antibody blockade or genetic knockout significantly inhibited AML progression by enhancing T-cell activity. Moreover, combining VISTA blockade with existing anti-PD-1 immunotherapy exhibited a synergistic anti-leukemia effect, offering a potential therapeutic strategy for AML patients.

AML poses a significant health challenge, with over 11,400 deaths annually in the United States alone. Despite advances in cancer treatment, the mainstay therapy for AML remains a combination of anthracycline and cytarabine, developed in the 1970s. Therefore, the identification of VISTA as a target for AML therapy presents a promising avenue for novel treatments.

The researchers extensively analyzed data from the Cancer Genome Atlas database, conducted studies with mouse models, examined bone marrow core biopsies from AML patients, and conducted various experiments to elucidate the role of VISTA in immune evasion in AML. Their findings suggest that VISTA mediates immune system evasion in AML by suppressing infiltrating T-cells within the leukemia microenvironment.