Mapping of B cell phenotypes in distinct immune neighborhoods in sarcoma

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Project Description

Immunotherapy has lately gained increased attention in sarcoma, but response rates are highly diverse. Therefore, it is essential to identify patient selection criteria and define whether the tumor microenvironment contains responsive immune cells. Earlier work originating from us in the sarcoma tumor microenvironment team has demonstrated that presence of CD20+ B cells is associated with superior patient survival, but only in a tumor microenvironment with less immunosuppressive characteristics.

The aim of our ongoing project is to map B cell phenotypes in distinct immune neighborhoods in sarcoma subtypes. Well-annotated, paraffin-embedded whole tissue slides from 200 patients treated at Karolinska University Hospital are characterized by multiplex immunofluorescence/immunohistochemistry using the Vectra®Polaris™ Automated Quantitative Pathology Imaging System. Multimarker-defined cell types and their cellular neighborhoods are explored by bioimage informatics. The collaboration with BIIF includes setting up more automated analyses of cell-cell interactions, non-random cellular enrichments, and characterization of immunosuppressive neighborhoods and immune deserts.

Significance: No major therapeutic advances have been made in sarcoma since the introduction of chemotherapy 30-40 years ago. Accordingly, there is an urgent need to improve, or fine-tune, the toxic multimodal treatments of today, and identify novel prognostic and/or response-predictive biomarkers.