The dual effect of interferon-γ in acute myeloid leukemia: A narrative review

Acute myeloid leukemia (AML) is a hematological malignancy representing a very rapid, uncontrolled growth of myeloid precursors in the BM and peripheral circulation. Studies on AML have highlighted the crucial role of IFN-γ therapy in immune surveillance, both promotive and inhibitory effects on leukemic cells, and regulation of the tumor microenvironment. However, there is a need for a comprehensive understanding of the dual effects of IFN-γ in AML. Thus, this review aimed to assess the dual effects of IFN-γ in AML. Literature searches were conducted in Pub Med, Google Scholar, and direct Google Search. The data was presented in tables and figures, with findings summarized through a narrative synthesis. Depending on the circumstances and stage of the disease IFN-γ shows two different activities in AML patients. First, IFN-γ enhances NK cells and CD8⁺ T lymphocyte functions, which collectively evoke antileukemic immunity. Another promising effect of IFN-γ includes the differentiation of myeloid cells, thereby possibly reducing the severity of leukemia. However, prolonged exposure to IFN-γ can activate Treg cells and inhibitory immunological checkpoints, which can help leukemia evade immune surveillance and encounter an immunosuppressive environment. Our review highlights IFN-γ's critical role in the complex interplay between the immune system and AML pathogenesis. Its dual role in both inhibiting and promoting leukemic processes has been highlighted. However, future pre-clinical and clinical studies should focus on the specific mechanisms by which IFN-γ impacts AML progression and treatment outcomes, with the goal of achieving curative results for patients.