''Thymocyte Selection-associated High Mobility Group Box Protein'' (''TOX'') is a protein necessary for [[T cell|T Cell]] persistence but also drives [[T cell exhaustion|T Cell Exhaustion]]. An increase in TOX expression is characterized by a weakening of the effector functions of the [[cytotoxic T cell|Cytotoxic T Cell]] and upregulation of inhibitory receptors on the cytotoxic T cells. TOX promotes the exhausted T cell phenotype through [[epigenetic|Epigenetics]] remodeling. [[PD-1]] is an inhibitory marker on T cells that increases when TOX is unregulated. This allows for cancerous cells to evade the cytotoxic T cells through upregulated expression of [[PD-L1]].

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Markers of effector functions that are decreased when TOX is overexpressed are [[KLRG1]], [[TNF|Tumor Necrosis Factor]], and [[IFN-gamma|Interferon Gamma]].

T-cell exhaustion does not occur when TOX is deleted from \CD8⁺ T cells, but the cells instead adopt the KLRG1⁺ terminal effector state and undergo [[apoptosis|Apoptosis]]. It was therefore proposed that TOX prevents this terminal differentiation and instead promotes exhaustion so that the T-cell has a slightly more sustained response.


Links:
* [[WIKIPEDIA - TOX|https://en.wikipedia.org/wiki/TOX]]