Application of Spatial Proteomics for Comprehensive Immune Monitoring in Cancer Clinical Trials 9251

Abstract Description Spatial proteomics can capture cell organization, providing deep insights into diseases and catalyze significant advancements in clinical diagnosis, treatment, and outcomes. The tumor microenvironment (TME) is an organized signaling network consisting of extracellular matrix (ECM), tumor cells, stromal cells, and immune cells. Tissue histopathology, particularly immunohistochemistry (IHC), remains the most frequently used modality to assess the TME. However, despite advances in histopathology, the complexity of the TME often leads to the loss of critical information about tumor function and clinical outcomes. New technologies for high-dimensional protein mapping within intact tissues, such as multiplexed ion beam imaging by time of flight (MIBI-TOF), are increasingly employed to reveal the functional encoding of the TME. MIBI uses secondary ion mass spectrometry to image metal-tagged antibodies in tissue samples. This allows for the simultaneous quantification of dozens of antibodies, even those present in low abundance, at a subcellular level within a single scan, offering precise insights into complex biological processes. We have utilized spatial omics tools to investigate immune tolerance in diverse contexts such as human neuropathology, peanut allergy immunotherapy, pulmonary arterial hypertension, and cancer. Here, we demonstrate the application of MIBI in large-scale cancer clinical trials to analyze panels of ∼30 biomarkers. Funding Sources 2U24CA224309 Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)