Transcriptional regulatory network for the establishment of CD8 T cell exhaustion.

Chronic infection with persistent antigenic stimulation results in the generation of exhausted CD8 T cells, which are considered defective effector CD8 T cells, and thus compromises effective immune responses. However, recent studies have illustrated that exhausted CD8 T cells may be purposely generated and maintained to provide mild immune responses against chronic infection or cancer, which can be safer over a long period of time than strong immune responses. Indeed, a specific population of exhausted CD8 T cells that behaves similarly to self-renewing stem cells and provides a continuous supply of exhausted CD8 T cells has been identified, indicating that this population can be considered progenitors of exhausted CD8 T cells.

Chemotherapeutic resistance of head and neck squamous cell carcinoma is mediated by EpCAM induction driven by IL-6/p62 associated Nrf2-antioxidant pathway activation.

Overexpression of epithelial cell adhesion molecule (EpCAM) has been associated with chemotherapeutic resistance, leads to aggressive tumor behavior, and results in an adverse clinical outcome. The molecular mechanism by which EpCAM enrichment is linked to therapeutic resistance via Nrf2, a key regulator of antioxidant genes is unknown. We have investigated the link between EpCAM and the Nrf2 pathway in light of therapeutic resistance using head and neck squamous cell carcinoma (HNSCC) patient tumor samples and cell lines.

Widespread expression of Sonic hedgehog (Shh) and Nrf2 in patients treated with cisplatin predicts outcome in resected tumors and are potential therapeutic targets for HPV-negative head and neck cancer.

Background: Sonic hedgehog (Shh) and Nrf2 play a critical role in chemotherapeutic resistance. These two genes have been found to be dysregulated in head and neck squamous cell carcinomas (HNSCC). The purpose of this study was to analyze the expression, function and clinical prognostic relationship of Shh and Nrf2 in HNSCC in the context of therapeutic resistance and cancer stem cells (CSCs).