OPG-Producing B Cells and RANKL-Expressing T Cells Define Immune Signatures Predictive of Bone Metastases in Breast...

Area of Science:

• Immunology
• Oncology
• Bone Biology

Background:

• Bone metastases are a significant complication of breast cancer (BC).
• The role of adaptive immune cells, particularly B cells, in bone metastasis is not fully understood.
• Understanding immune mechanisms is crucial for developing novel therapeutic strategies against BC bone metastases.

Purpose of the Study:

• To elucidate the role of CD19+ B cells in modulating bone remodeling and breast cancer metastasis.
• To investigate the therapeutic potential of B cells in preventing or treating bone metastases.
• To identify immune biomarkers associated with BC bone metastasis.

Main Methods:

• Utilized murine models of metastatic (4T1) and non-metastatic (67NR) mammary tumors.
• Employed functional assays, adoptive B cell transfer, and molecular analyses (including transcriptomics).
• Retrospective analysis of a human cohort correlating immune cell infiltration with bone metastasis.

Main Results:

• CD19+ B cells from non-metastatic tumor-bearing mice secreted osteoprotegerin (OPG), suppressed bone resorption, and counteracted T cell-mediated osteolysis.
• Adoptive transfer of OPG-producing B cells into metastatic tumor-bearing mice preserved bone, reduced RANKL, inhibited metastasis, and limited tumor growth.
• Human data showed RANKL+ lymphocyte infiltration correlated with bone metastases, while OPG+ infiltration was associated with metastasis-free cases.

Conclusions:

• A novel B cell-driven axis involving OPG secretion restrains osteolysis and breast cancer progression.
• CD19+ B cells, when primed appropriately, possess therapeutic potential against bone metastases.
• Immune phenotypes, specifically OPG+ B cells and RANKL+ lymphocytes, serve as prognostic biomarkers for BC bone metastasis.