Digital Spatial Profiling (DSP) technology uncovers microenvironmental remodeling and immune dynamics in T-DXd resistant metastatic breast cancer

Glori Das; Matthew Vasquez; Ji-Hoon Lee; Yuan Gao; Jilun Zhang; Jenny Chang; Xiaoxian Li; Hong Zhao; Stephen T. C. Wong

doi:10.1117/12.3049442

21 October 2024 Digital Spatial Profiling (DSP) technology uncovers microenvironmental remodeling and immune dynamics in T-DXd resistant metastatic breast cancer

Glori Das, Matthew Vasquez, Ji-Hoon Lee, Yuan Gao, Jilun Zhang, Jenny Chang, Xiaoxian Li, Hong Zhao, Stephen T. C. Wong

Author Affiliations +

Proceedings Volume 13186, SPIE Translational Biophotonics + Additive Manufacturing for Photonics 2024; 131861W (2024) https://doi.org/10.1117/12.3049442
Event: SPIE Translational Biophotonics + Additive Manufacturing for Photonics, 2024, Houston, Texas, United States

Conference Poster

Abstract

NanoString GeoMX Digital Spatial Profiling (DSP) is an emerging optical technology for spatial multi-omics. DSP utilizes probes attached to UV-photocleavable, fluorescent oligonucleotide barcodes indicating target identity and location. These barcodes are counted to quantify gene expression. This high-throughput, single-cell resolution tool exemplifies how optics can elucidate disease mechanisms. Our study employed DSP to understand T-DXd resistance in metastatic breast cancer (mBC). T-DXd is an antibody-drug conjugate that is standard of care in mBC. Patients have few options if T-DXd fails; uncovering resistance mechanisms is crucial for developing life-saving therapies. We used GeoMX DSP to investigate tumor-immune interactions in T-DXd responsive and resistant patient samples. We captured spatially diverse tumor-dense and tumor-sparse regions of interest for proteomics analysis. We found that local stromal remodeling and decreased killer T-cell infiltration are T-DXd resistance characteristics. These results show promise for helping T-DXd resistant-patients and highlight the importance of optical imaging in drug discovery.

(2024) Published by SPIE. Downloading of the abstract is permitted for personal use only.

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Glori Das, Matthew Vasquez, Ji-Hoon Lee, Yuan Gao, Jilun Zhang, Jenny Chang, Xiaoxian Li, Hong Zhao, and Stephen T. C. Wong "Digital Spatial Profiling (DSP) technology uncovers microenvironmental remodeling and immune dynamics in T-DXd resistant metastatic breast cancer", Proc. SPIE 13186, SPIE Translational Biophotonics + Additive Manufacturing for Photonics 2024, 131861W (21 October 2024); https://doi.org/10.1117/12.3049442

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