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Spatially resolved profiling of extracellular vesicles in tissues with Spatial-EV-seq
Qianxi Wen1,2, Xing Na1, Yuming Lu1
1The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, State Key Laboratory of Physical Chemistry of Solid Surfaces, Fujian Key Laboratory of Chemical Biology, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China.
Spatial-EV-seq maps extracellular vesicles (EVs) in their native environment, revealing how their location impacts cancer immunity and therapeutic response. This method aids in understanding EV roles for better diagnostics and treatments.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Extracellular vesicles (EVs) are crucial biomarkers but current methods lack spatial context.
- Understanding EV spatial distribution is key to deciphering cell-cell communication in disease.
Purpose of the Study:
- To develop a novel method, Spatial-EV-seq, for in situ spatial profiling of EVs.
- To investigate the role of EV spatial distribution in anti-PD1 therapy resistance in breast cancer.
Main Methods:
- Spatial-EV-seq utilizes an antibody-engineered capture interface and aptamer-based rolling circle amplification.
- Combines ultrasensitive EV profiling, molecular subtyping, and spatial mapping with transcriptomics.
- Applied to an anti-PD1 breast cancer mouse model.
Main Results:
- Spatial-EV-seq successfully mapped EVs and their molecular profiles within the tumor microenvironment.
- Identified spatially orchestrated immunosuppressive zones enriched with PDL1+ EVs, leading to CD8+ T cell dysfunction.
- Demonstrated that PDL1+ EV-depleted regions maintained immune competence and therapeutic sensitivity.
Conclusions:
- Spatial-EV-seq provides high-resolution insights into EV-mediated communication networks.
- Reveals a mechanism of immune evasion driven by EV spatial organization in cancer.
- Unlocks new possibilities for precision diagnostics and EV-targeted therapeutics.