DNA-barcoded signal amplification for imaging mass cytometry enables sensitive and highly multiplexed tissue imaging
Tsuyoshi Hosogane1,2,3, Ruben Casanova1,2, Bernd Bodenmiller4,5
1Department of Quantitative Biomedicine, University of Zurich, Zurich, Switzerland.
Insights
Imaging mass cytometry (IMC) now detects low-abundance markers using signal amplification by exchange reaction (immuno-SABER). This advance allows detailed imaging of the tumor immune microenvironment, revealing previously undetectable immune cell markers.
Area of Science:
- Biomedical Imaging
- Immunology
- Molecular Biology
Background:
- Imaging mass cytometry (IMC) provides high-resolution spatial protein expression data.
- Detecting low-abundance markers with IMC remains a challenge.
- Understanding the tumor immune microenvironment is crucial for cancer research.
Purpose of the Study:
- To enhance IMC's capability for detecting low-abundance protein markers.
- To apply the enhanced method for analyzing the tumor immune microenvironment in melanoma.
Main Methods:
- Incorporation of signal amplification by exchange reaction (SABER) into IMC, termed SABER-IMC.
- Simultaneous imaging of 18 markers using immuno-SABER and 20 markers without amplification.
- Application to human melanoma samples.
Main Results:
- SABER-IMC successfully enabled the detection of low-abundance immune cell phenotypic markers.
- Markers such as T cell co-receptors and their ligands, previously undetectable by IMC, were identified.
- Detailed spatial protein expression patterns in the tumor immune microenvironment were visualized.
Conclusions:
- SABER-IMC significantly expands the utility of IMC for deep profiling of the tumor immune microenvironment.
- This method allows for the identification of critical, low-abundance immune cell markers.
- SABER-IMC offers a powerful tool for advancing cancer immunology research.
Abstract:
Imaging mass cytometry (IMC) is a highly multiplexed, antibody-based imaging method that captures heterogeneous spatial protein expression patterns at subcellular resolution. Here we report the extension of IMC to low-abundance markers through incorporation of the DNA-based signal amplification by exchange reaction, immuno-SABER. We applied SABER-IMC to image the tumor immune microenvironment in human melanoma by simultaneous imaging of 18 markers with immuno-SABER and 20 markers without amplification. SABER-IMC enabled the identification of immune cell phenotypic markers, such as T cell co-receptors and their ligands, that are not detectable with IMC.
