Identification of a Unique B Cell Niche Population in Breast Cancer Bone Metastasis

Abstract

Breast cancer patients with bone metastasis have high mortality rates, as tumor cells can exploit immune cells in the bone marrow (BM) niche to support their own proliferation and maintenance through unknown mechanisms. Distinguishing between pro-tumor and anti-tumor immune cell populations in BM is essential for developing more targeted immunotherapies that confer more effective clinical benefit, while also limiting adverse effects for patients. From the Kang Lab’s preliminary single cell RNA sequencing (scRNA-seq) study of the BM metastatic niche, I observed a distinct, niche-specific CD19+ B cell population that also expresses the surface markers Btla and Cr2. Through flow cytometry and immunostaining methods, we confirmed that our CD19+ Btla+ Cr2+ population is enriched at the boundary edge between tumor and surrounding BM tissue and may be classified as an immature B cell. Furthermore, we find that when tumor cells are co-cultured with CD19+ Btla+ Cr2+, they can decrease CD19+ Btla+ Cr2+ proliferation and Cr2 expression in certain conditions. In other cases, tumor cells are also capable of inducing Btla expression in CD19+ populations that do not originally express our two surface markers (CD19+ Btla- Cr2-). These results suggest that tumor cells mediate their own survival by manipulating the expression of B cell surface markers associated with B cell activation and proliferation. This study ultimately aims to enhance the field’s understanding of tumor cell-B cell niche interactions. These insights will contribute to the development of effective B cell-based immunotherapies that can counteract tumor immune escape mechanisms, even in the heterogeneous BM tumor microenvironment.