Currently, the single best predictive biomarker of response to anti-PD1 monotherapy is PD-L1 expression as assessed by immunohistochemical staining of archived or fresh tissue. Current workflows for PD-L1 assessment in tissue are labor and time consuming, are not infallible (inconclusive results in a fraction of image guided biopsies) and are associated with morbidity and are thus rarely performed serially. Rapid on site assessment of cellular, rather than tissue, specimens obtained through fine needle aspiration (FNA) could not only circumvent these bottlenecks but also enable more comprehensive and serial profiling of the tumor microenvironment to obtain the most up-to-date information of a rapidly changing microenvironment during tumor evolution and therapy. The goal of this project is to further develop and validate the new FAST-FNA technology for rapid biomarker discovery and validation in HNSCCs. There are two main aims.
In aim 1 we will develop and validate existing and new biomarkers in FNA samples of HNSCC patients (n=100). Specifically we will I) develop and validate new predictive immunotherapeutic biomarkers and ii to determine how well the new FAST-FNA scores correlate with the CPS scores of PD-L1. The goal of the second aim is to translate the above FAST-FNA technology to serial FNA analyses in HNSCC patients receiving anti-PD1 immunotherapy (with or without chemotherapy; n=100). FNA sampling will be performed pre- and on-treatment in order to capture changes in the tumor microenvironment. As the HNSCC field shifts toward increased biomarker testing, we find an unmet clinical need to develop advanced cellular diagnostics in HNSCCs, which will facilitate rapid biomarker analysis, guide therapies and provide ?real time? assessment of clinical response.
Existing analysis of HNSCC cancer tissues obtained by core biopsy is limited in many aspects. We have developed a new immune and cancer cell profiling technology based on cellular immunocycling. Using fine needle aspirates (FNA) rather than more invasive core biopsies, this method allows frequent and serial profiling on the composition of the tumor microenvironment in HNSCC patients undergoing immunotherapy.