Breast cancer immunobiology driving immunotherapy: vaccines and immune checkpoint blockade

Abstract

Breast cancer is immunogenic, and infiltrating immune cells in primary breast tumors convey important clinical prognostic and predictive information. Furthermore, the immune system is critically involved in clinical responses to some standard cancer therapies. Early breast cancer vaccine trials have established the safety and bioactivity of breast cancer immunotherapy, with hints of clinical activity. Novel strategies for modulating regulators of immunity, including regulatory T cells, myeloid-derived suppressor cells and immune checkpoint pathways (monoclonal antibodies specific for the cytotoxic T-lymphocyte antigen-4 or programmed death), are now available. In particular, immune checkpoint blockade has enormous therapeutic potential. Integrative breast cancer immunotherapies that strategically combine established breast cancer therapies with breast cancer vaccines, immune checkpoint blockade or both should result in durable clinical responses and increased cures.

Keywords::

• breast cancer immunity
• breast cancer vaccine
• clinical trials
• immune checkpoint blockade
• immune tolerance
• immunotherapy
• tumor microenvironment

Financial & competing interests disclosure

This work was supported by the Department of Defense (Clinical Translational Research Award W81XWH-07-1-0485), the American Cancer Society (RSG CCE 112685), Genentech Inc. and the V Foundation. LA Emens receives research funding from Genentech, Inc., and has received honoraria for participating on regional advisory panels for Genentech, Inc., Roche Inc. and Bristol-Myers Squibb. Under a licensing agreement between Biosante, Inc. and the Johns Hopkins University, the University is entitled to milestone payments and royalty on sales of the GM-CSF-secreting breast cancer vaccine. The terms of these arrangements are being managed by the Johns Hopkins University in accordance with its conflict of interest policies. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.