The double-edged role of interferon gamma in cancer immunity.

Interferon-gamma (IFN-γ) is a pivotal cytokine that coordinates the immune response to infections caused by viruses and intracellular pathogens. Knockout (KO) mice lacking IFN-γ exhibited a significant reduction in the capacity of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells to eliminate tumor cells, resulting in accelerated tumor growth and metastasis. These findings underscore the key role of IFN-γ in regulating the antitumor immune response. However, many advanced tumors exhibit dysregulated IFN-γ signaling, which exerts direct protumoral and immunosuppressive effects, thereby allowing cancer cells to evade immune surveillance and promoting cancer progression. This dual role of IFN-γ in regulating cancer immunity has limited its therapeutic use in cancer. Understanding the specific conditions under which IFN-γ has an antitumoral or a protumoral role is a challenge for optimizing its use in cancer therapy.