Survival is rare in the 20-50% of oral cavity squamous cell carcinoma (OC) patients whose cancer recurs after standard-of-care surgical resection and adjuvant chemoradiotherapy. OC tumors are highly infiltrated by T cells and other immune cells, but the immunosuppressive tumor environment limits their antitumor activity. Immune checkpoint blockade (ICB) is a type of immunotherapy that reactivates immune cells inside the tumor, driving interest in ICB treatment prior to resection in OCSCC, i.e., neoadjuvant ICB. The potential clinical benefits of neoadjuvant ICB include reduction in the volume of resected tumor tissue - possibly even tumor clearance - and decreased rates of recurrence/metastasis ...

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Survival is rare in the 20-50% of oral cavity squamous cell carcinoma (OC) patients whose cancer recurs after standard-of-care surgical resection and adjuvant chemoradiotherapy. OC tumors are highly infiltrated by T cells and other immune cells, but the immunosuppressive tumor environment limits their antitumor activity. Immune checkpoint blockade (ICB) is a type of immunotherapy that reactivates immune cells inside the tumor, driving interest in ICB treatment prior to resection in OCSCC, i.e., neoadjuvant ICB. The potential clinical benefits of neoadjuvant ICB include reduction in the volume of resected tumor tissue - possibly even tumor clearance - and decreased rates of recurrence/metastasis due to systemic immunity. In collaboration with Genentech, we are conducting a phase 2 clinical trial of neoadjuvant tiragolumab plus atezolizumab, a novel ICB combination, in OC. In the proposed study, we will extensively analyze biospecimens from patients on the trial to identify biomarkers predicting response and to determine how treatment affects immune cells in responding and nonresponding patients. This study is significant because it will determine whether tiragolumab plus atezolizumab has the potential to increase the OCSCC patient population that benefits from neoadjuvant ICB and thus warrants further clinical investigation. Importantly, our extensive analyses of biospecimens, which includes functional profiling of tumor-specific T cells, will allow us to identify mechanisms of response and resistance to improve cure rates for OCSCC via data-driven selection of ICB combinations. Successful completion of our aims has the potential to change clinical practice and thus have a major impact on cancer.

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