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The power of spatial biology lies in the integration of multiple scales of information from subcellular to tissue scale. Until recently, spatial analysis of protein biomarkers in tissues was limited to a few markers at a time using traditional IHC colorimetric or fluorescent readout. Here, we demonstrate the ability of NanoString’s CosMx™ Spatial Molecular Imager (SMI) platform to quantify more than 70 proteins encompassing key targets in immuno-oncology and tumor biology, localize the proteins and analyze protein expression at a single cell level. Key to the technology is the use of fully automated fluidics and imaging systems, short turnaround time, and high sensitivity. The CosMx protein assay has been optimized for FFPE samples, which represent the largest collection of biospecimens available for clinical investigation. To that end, we explored the utility of CosMx spatial proteomics on a series of clinical samples from cancer patients, including the Serial Measurements of Molecular and Architectural Response to Therapy (SMMART) trial, across multiple cancer types. CosMx SMI’s high-level protein multiplexing capabilities enabled spatial analysis of metastatic tumors in response to personalized treatment for a single patient over time. Combining spatial data obtained from both CosMx RNA and protein assays on the same sample reveals distinct regions of Tumor Associated Macrophages and their interactions with tumor cells in some samples. Detection of phosphoproteins also allows for analysis of the impact of kinase inhibitor treatment on the spatial environment in longitudinal biopsies. The highly-multiplexed spatial analysis of proteins in longitudinal metastatic breast cancer biopsies under therapeutic pressure provides a unique opportunity to understand evolution of tumors and develop and implement therapeutic approaches that can directly target mutations arising in the tumor cells while effectively engaging the immune system. FOR RESEARCH USE ONLY. Not for use in diagnostic procedures. Citation Format: Zachary R. Lewis, Brian Birditt, Emily Brown, Kan Chantranuvatana, Brian Filanoski, Chris Corless, Tiên Phan-Everson, Gary Geiss, Tyler Hether, Evie Hobbs, Brett Johnson, Taylor Kelley, Charles Lopez, Rhonda Meredith, Anastasiya Olson, Giang Ong, Mithra Korukonda, Erin Piazza, Jason Reeves, Alyssa Rosenbloom, Kiara Siex, Hye Son Yi, Edward Zhao, Joseph M. Beechem, Gordon Mills. Single cell spatial molecular imaging of 76-plex proteins in clinical cancer samples in response to personalized treatment. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5641. |
