Expression pattern, regulation, and clinical significance of TOX in breast cancer

AbstractThymocyte selection-associated high mobility group box protein (TOX) is a transcription factor implicated in the regulation of T cell exhaustion during chronic infection and cancer. While TOX is being targeted for cancer immunotherapy, limited information is available about its significance in breast cancer and other solid tumors. We performed a comprehensive analysis ofTOX gene expression, its epigenetic regulation, protein localization, relation to tumor infiltrating immune cell composition, and prognostic significance in breast cancer using publicly available datasets. Our results suggest an inverse correlation betweenTOX expression and DNA methylation in tumor cells. However, its expression is elevated in tumor infiltrating immune cells (TIICs), which may compensates for the totalTOX levels in the tumor as a whole. Furthermore, higherTOX levels in tumors are associated with T cell exhaustion signatures along with presence of active inflammatory response, including elevated levels of T cell effector cytokines. Survival analysis also confirmed that higher expression ofTOX is associated with better prognosis in breast cancer. Therefore, expression ofTOX may serve as a novel prognostic marker for this malignancy.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research