Establishment of a Zebrafish model to study the role of SIGMAR1 in oral cancer-immunity cycle

Abstract

Squamous cell carcinoma of the oral cavity (OSCC) is a malignant tumor and the leading cause of mortality among all head and neck cancers. It is an immunosuppressive disease, metastatic, and resistant to conventional immune-based therapies. Thus, there is a critical need for more effective immunotherapies for OSCC. Recent studies have demonstrated that the Sigma-1 Receptor (Sig-1R), a biomarker of worse prognosis, is involved in the immunoregulation between the antitumor immunity pathway (PD-1/ PD-L1), in the progression and resistance of several cancers. Surprisingly, the role of Sig-1R in OSCC biogenesis is unclear to date. So, the hypothesis is that Sig-1R modulates the tumor immune response and OSCC aggressiveness. To address this hypothesis, aim one will establish Zebrafish as a model to study oral cancer development and determine the role of Sig-1R Knockdown in OSCC biogenesis. Posteriorly we intend to evaluate the impact of the gene silencing in a preclinical study using Zebrafish as an animal model; and dissect at the mechanistic level the functional role of Sig-1R in the tumor immune response in vivo: focus on cancer-immunity cycle targets. The collective proposed studies may reveal a previously uncharacterized role of the Sig-1R in OSCC tumors. These studies will significantly add to our understanding of the OSCC development and potentially identify novels immune-based biomarkers for the patients with poor outcome. (AU)