Immunomodulatory Role of T Cell Immunoglobulin and Mucin Domain-3 in Cancer

Immune checkpoint inhibitors are one of the most promising areas in oncoimmunology research. T cell immunoglobulin and mucin domain-3 (TIM-3) expression has been linked to the advanced stages with reduced survival in several types of cancer, primarily due to its association with the dysfunction in T cells. Thus, TIM-3 is an interesting target in designing advanced therapy for cancer. TIM-3 has been implicated in resistance to immunotherapy on account of its involvement in T cell exhaustion. Identifying small molecule inhibitors targeting TIM-3 with high affinity, either alone or in combination with either chemotherapy or other types of immunotherapies could significantly enhance the life span, overcoming the resistance and overall immune response in therapy. TIM-3 pathway is multidimensional in terms of canonical signaling with varied expression of immune cells and diverse ligands and modulates the immune response. This may include restoration of the functioning of killer T lymphocytes and natural killer cells (NK cells) and likely promise better results in cancer immunotherapy. In this review, we will discuss the immunomodulatory role of TIM-3 in cancer, with special emphasis on lymphoma and solid tumors, and their role in diverse immune cells in tumorigenesis and inflammation.