Multiplexed cellular fluorescent imaging in head and neck squamous cell carcinomas (HNSCC) for different markers to predict patient specific response rates to immunotherapy and for mapping of the tumor microenvironment (TME).
Mentor: Ralph Weissleder, M.D. (Massachusetts General Hospital)
A variety of different immunotherapies have proven successful in treating a fraction of cancers. For example, immune checkpoint inhibitors are efficacious in 20-30 % of patients with lung, head and neck and other cancers. The reasons for different response rates remain ill understood but have been associated with differing tumor mutational burden, variable PD-L1 expression, existence of hot or cold tumors, tumor heterogeneity and macrophage mediated removal of antibodies. From a clinical perspective, there is thus a need to profile each patient’s tumor microenvironment in order to i) predict response rates and ii) follow treatment efficacy. Such studies are especially critical given the relatively high costs and side effects of many immunotherapies. Because peripherally circulating immune cells are an unreliable predictor of the TME, core biopsies are often performed, e.g. for immune cell profiling. One critical aspect with core and fine needle aspirates is the inability to quickly measure the dozens of markers required for immune cell identification. A newly developed multiplex cycling technique (FAST) potentially solves this problem. The goal of the current study is to adapt the FAST technique to head and neck cancer samples. The specific aims are to i) optimize and validate different phenotyping markers for tissue sections and ii) develop and validate newly emerging markers of treatment response (e.g. B cells markers; Nature ref).
Figure 1. Example of stained mice tumors with CD4, CD8, TCRb markers. Only one marker per channel is visible. Source: