Abstract 6464: Spatial mapping of the tumor microenvironment for combination therapy design

Abstract Cancer immunotherapy is a promising treatment for many forms of cancer, however only a small subset of patients benefit, and relapse/recurrence frequently occurs due to various resistance mechanisms. To overcome this challenge combinatorial therapeutic strategies are needed targeting multiple steps of the cancer-immunity cycle to achieve long-term efficacy in a large population of cancer patients. It is now known that DNA damage activates the innate immune response and improves immune checkpoint blockade (ICB) efficacy. Combination immunotherapy can target several immunosuppressive elements in the tumor microenvironment and activate multiple steps of the cancer-immunity cycle. For developing an effective combination treatment strategy, including ICB with various other therapeutic modalities, we need to first understand the diverse expression pattern of various factors within tumor immune microenvironment. Multiplex immunofluorescence (mIF) is an important tool for profiling protein expression patterns in tumor tissues. This can provide a framework to understand the sensitivity to a particular combination of therapies and identify potential predictive biomarkers. Here we show spatial proteomics profiling of a diverse range of biomarkers in human colon adenocarcinoma tissue. Our findings demonstrate that spatial proteomics can be tailored to precision oncology using artificial intelligence to predict a patient’s response to combination treatment strategies. The Cell DIVE Multiplex Imaging Solution in combination with AI-based image processing software, AIVIA delivers a comprehensive solution for exploring immune landscape of tumor tissue. The broad portfolio of robust IHC- validated antibodies from Cell Signaling Technology (CST) enables the detection of key proteins in the tumor microenvironment (TME). Here, we demonstrate multiplexed Cell DIVE imaging using a novel CST panel to probe human colon adenocarcinoma. The availability of cell type specific biomarkers, combined with the ability to interrogate using multiplexed tissue imaging, provides unprecedented and novel insights and spatial resolution of diverse cell populations in the TME. Citation Format: Arindam Bose, Susan Keezer, Emily Quann Alonzo, Sophie Struble, Jeremy Fisher, Matthew Norton, Richard A. Heil-Chapdelaine, Natasha F. Diaz Granados, Vasundhara Agrawal. Spatial mapping of the tumor microenvironment for combination therapy design [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6464.