TIM-3+ Macrophages: Insights into Their Role in Cancer and Inflammation

T-cell immunoglobulin and mucin domain 3 (TIM-3), a well-known immune checkpoint molecule, is increasingly recognized for its regulatory functions beyond T cell exhaustion, particularly in macrophages. Recent advances have revealed the important role of this molecule in various pathological and physiological conditions. The demand for a comprehensive study of TIM-3 is increasing, particularly as a result of ongoing clinical trials targeting TIM-3 in oncology. This review is devoted to the role of TIM-3 in macrophage biology, focusing on associations between TIM-3 expression and macrophage polarization states and functional activity, as well as its involvement in the pathogenesis of different diseases and reproductive immunology. The review examines known effects and molecular mechanisms by which TIM-3 regulates macrophage functional phenotype and the contribution of TIM-3-expressing macrophages to cancer, pregnancy, inflammation, infectious and autoimmune diseases, and fibrosis. Findings highlight the controversial role of TIM-3 in the regulatory function of macrophages and suggest that TIM-3 functions differently depending on the context. The review also touches on gaps and unexplored parts of the topic. A summary of current data allows us to conclude that TIM-3 is an important modulator of macrophage functions and can be considered a potential therapeutic target in various pathological conditions.