Unlocking the potential of TIGIT in enhancing therapeutic strategies for acute myeloid leukemia through combined azacitidine therapy

Immune checkpoint blockade (ICB) therapy has emerged as a pivotal advancement in cancer treatment, yet its efficacy varies among patients and resistance can develop. This study focuses on TIGIT, a newly identified immune checkpoint, to explore its expression, prognostic significance, and therapeutic potential in hematologic malignancies, particularly acute myeloid leukemia (AML). In this study, we found TIGIT highest expression levels in bone marrow and lymphoid tissues, with enrichment in immune cells such as NK-T cells and regulatory T cells (Tregs). A prognostic model incorporating TIGIT expression and other immune-related genes effectively stratified AML patients into high-risk and low-risk groups, with the former displaying significantly shorter overall survival times. Our model outperformed traditional prognostic factors, highlighting TIGIT's potential as a superior predictive biomarker. Additionally, our in vitro and in vivo studies showed that combining tiragolumab with azacitidine (AZA) synergistically enhanced anti-tumor efficacy, reducing tumor burden and extending survival in a murine AML model. Our findings underscore TIGIT's role in hematologic malignancies and its potential as a therapeutic target in AML. The combination of AZA with TIGIT inhibition offers a promising new approach for AML treatment, warranting further clinical evaluation.