Immunotherapies & Personalized Vaccines
Jing Yang (MCC)
Daniel Hollern (Salk)
Current immune checkpoint inhibitors generally only generate anti-tumor responses in about 15% breast cancer patients already presenting recurrent metastatic lesions. Here we propose to establish new breast tumor models to study whether and how crosstalk between tumor cells and B-cells impact anti-tumor immunity and tumor responses to immune checkpoint inhibitors. Results from the proposed research could lead to publications and extramural funding to further this study in the short term. Our proposed research also has direct therapeutic implication in the long run. Currently, immune checkpoint inhibitors are largely given to breast cancer patients that have failed conventional chemotherapies and present metastatic lesions. Since conventional chemotherapy cannot kill dormant disseminated tumor cells that are not proliferating, many breast cancer patients that are considered “high risk” for metastatic recurrence can only wait and see whether their breast cancer will come back as distant metastases. Yet patient data tells us that B cell recognition of metastasis leads to longer survival. If our proposed research is successful, it would provide much needed new treatment option for high-risk breast cancer patients. This is especially important for triple-negative breast cancer, which no other targeted therapy is currently available to prevent metastasis recurrence. In addition, our research also explores new molecular mechanisms that help dormant tumor cells to evade immune surveillance in distant organs. Uncovering new molecular targets to boost anti-tumor immunity could significantly improve patient responses to immune checkpoint inhibitors. Therefore, our research could also lead to reducing the mortality associated with metastatic breast cancer.