The study of the tumor ecosystem and its cell-to-cell communications is essential to enable an understanding of tumor biology, to define new biomarkers to improve patient care, and ultimately to identify new therapeutic routes and targets.To study and understand the workings of the tumor ecosystem (TME), highly multiplexed image information of tumor tissues is essential. Such multiplexed images will reveal which cell types are present in a tumor, their functional state, and which cell-cell interactions are present. To enable multiplexed tissue imaging, we developed imaging mass cytometry (IMC). IMC is a novel imaging modality that uses metal isotopes of defined mass as reporters on antibodies and currently allows the visualization of over 50 proteins simultaneously on tissues with subcellular resolution. In the near future, we expect to be able to visualize over 100 proteins. Thus highly specific, reproducible and deeply validated antibodies are essential for IMC and any multiplexed antibody based method.
We applied IMC for the analysis of hundreds of breast cancer samples in a quantitative manner. Our analysis with a novel computational pipeline reveals a surprising level of inter and intra-tumor heterogeneity and identified new diversity within known human breast cancer subtypes, as well as a variety of stromal cell types that interact with them. Furthermore, we identified cell-cell interaction motifs in the tumor microenvironment correlating with clinical outcomes of the analyzed patients.
In summary, our results show that IMC provides targeted, high-dimensional analysis of cell type, cell state and cell-to-cell interactions within the TME at subcellular resolution. Spatial relationships of complex cell states of cellular assemblies can be used as biomarkers. We envision that IMC will enable a systems biology approach to understand and diagnose disease and to guide treatment.
Learning Objectives:
- Learn about the novel imaging technique imaging mass cytometry (IMC)
- Understand how antibody quality impacts highly multiplexed techniques
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