Research Project
Full description Immune checkpoint inhibitor (ICI) therapy has had limited success (less than 30%) in treating metastatic recurrent Head and Neck Oropharyngeal Squamous Cell Carcinomas (OPSCCs). We postulate that spatial determinants in the tumor play a critical role in cancer therapy outcomes. Using advanced spatial proteogenomic analysis on the patient's recurrent OPSCC tumors we demonstrate that: (i) unbiased tissue clustering based on spatial transcriptomics (ST-seq) successfully detected tumor cells and enabled the investigation of phenotypic traits such as proliferation or drug-resistance genes in the tumor's leading-edge and core; (ii) spatial proteomic imagining used in conjunction with ST-seq can resolve the profiling of tumor infiltrating immune cells, (iii) ST-seq data allows for the discovery and ranking of clinically relevant alternative medicines based on their interaction with their matching ligand/receptor. Importantly, when the spatial profiles of ICI pre- and post-failure OPSCC tumors were compared, they exhibited identical PD-1/PD-L1low and VEGFAhigh expression, suggesting that these new tumors were not the product of ICI resistance but rather of Lenvatinib dose reduction due to complications.