CD8 + T cell dysfunction by TOX intoxication: a protumorigenic event in the tumor microenvironment

Accumulating evidence suggests the role of cellular components in achieving antitumor to protumor microenvironments. Among the various types of cells within the tumor niche, the state of CD8⁺ T cells apparently changes from cytotoxic T effector cells and memory T cells to exhausted CD8⁺ T cells. These changes in the phenotype of CD8⁺ T cells promote the protumor microenvironment. Recently, comprehensive experimental data delineated the role of thymocyte selection-associated high-mobility group-box protein (TOX), which regulates the transcriptional process and epigenetic remodeling, with implications in tumor and chronic viral infections. This perspective summarizes the molecular mechanisms that link CD8⁺ T cells, TOX, and transcriptional and epigenetic reprogramming as well as future directions for determining new avenues of cancer therapeutics.