MAP-BC · Mapping antigenic niches of tumor-infiltrating B cells in triple-negative breast cancer

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Project objective

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtypes, with limited treatment options and poorer survival. The introduction of immunotherapy has improved outcomes, yet only a fraction benefit. Current biomarkers do not reliably predict response, highlighting the urgent need for better tools. Most immunotherapies target T cells. However, tumor-infiltrating B cells and plasma cells (TIL-Bs) have been linked to improved responses to immunotherapy. What these cells recognize and where these interactions occur remains unclear, although early evidence suggests that spatial context may influence response. Until these gaps are addressed, the role of B cells in tumor immunity will remain unresolved, limiting a full understanding of their therapeutic contribution. In this context, the main aim of MAP-BC is to develop an integrated pipeline that links TIL-B clones with their antigens and spatial niches, which will provide mechanistic insight and predictive value for immunotherapy response in TNBC. First, I will generate recombinant antibodies from spatially-resolved B-cell clones in pre-treatment biopsies. I will use SpatialVDJ, an in-house spatial transcriptomics tool that captures full length B-cell receptors within the tissue. These antibodies will allow functional characterization of B-cell clones in the tumor. Next, I will integrate multiple antigen discovery platforms, including a novel in situ platform that identifies antigens directly in tissue. Finally, I will define “spatial antigenic niches” linking discovered antigens, their cognate B-cell clones, and surrounding microenvironment, and test if these features are associated with therapy response. MAP-BC will help unravel TIL-B´s role in immunotherapy and identify clinically relevant B-cell clones and their antigens, while providing a platform for further discovery. The project will lay the groundwork for predictive biomarkers and open new avenues toward B cell–based cancer immunotherapy.

Original text from CORDIS.

Participants

• KAROLINSKA INSTITUTET · STOCKHOLMCoordinatorSweden

Links

• View on CORDIS
• DOI: 10.3030/101274291