Unraveling the tumor microenvironment architecture by multispectral imaging
The natural history of cancer involves interactions between the tumor and the immune defense mechanism of the host. The crucial role of the patient’s own immune system on clinical outcome is demonstrated by the immunological characterization of the tumor microenvironment. The analysis of type, location and density of tumor infiltrating immune cell components has identified immune cell types that can be either beneficial or harmful to patients showing also that immune cells can infiltrate the core (center) of the tumor and/or remain located in peritumoral areas and that lymphocytic infiltration of tumor or peritumoral tissue can be a favorable prognostic factor in a range of tumor types. In order to better understand the tumor microenvironment and its architecture, recent advances in the field of tissue imaging resulted in the development of multispectral imaging and analysis of up to six immunofluorescence markers within intact tissue sections. This novel technique combines imaging with spectroscopy allowing quantitative assessment of cellular phenotype and activity in a way similar to flow cytometry, while simultaneously providing tissue context and information about cell-to-cell usually difficult or impossible to obtain by other methods. We developed different 7-plex immunofluorescence multispectral panels and applied this novel technology to multiple tumor types in order to identify and quantify the densities of different immune cell subtypes. Furthermore, we have developed an analytical pipeline for first- and second-order spatial analysis of multispectral imaging data, which enables a high-definition characterization of the tumor microenvironment architecture including the spatial distribution of the different immune cell subtypes.
INSERM UMRS1138 Integrative Cancer Immunology / Cordeliers Research Center