Recent studies of
tumor lymphocytic immune infiltrates in
breast cancer have suggested an improved prognosis associated with increasing levels of tumor-infiltrating lymphocytes (TIL).
Triple-negative breast cancer (TNBC) is the
breast cancer subtype that has the greatest incidence of patients with a robust
tumor immune infiltrate, although it is still a minority of patients. Elevated levels of either intratumoral or stromal T cells are associated with an improved overall survival (OS) and disease-free survival (DFS) in TNBC as compared with other
breast cancer subtypes. TNBC may be immunogenic for several reasons. Subtypes of TNBC have a significant number of genetic mutations, and the immune system may see the aberrant
proteins encoded by these mutations as foreign. Moreover, TNBC is associated with a prognostic gene signature that also includes B cells.
Antibodies secreted by B cells may bind to
tumor antigens and amplify the adaptive immune response that has already been initiated in the
tumor. New immune modulatory agents, including
immune checkpoint inhibitors, have shown activity in immunogenic
tumors such as
melanoma and
bladder cancer and have recently been tested in TNBC. The clinical response rates observed, patterns of response, and adverse event profiles are similar to what has been described in
melanoma where this class of agents has already been approved for clinical use in some cases. Lessons learned in assessing the immunogenicity of TNBC, potential mechanisms of immune stimulation, and response to immune modulatory drugs lay the foundation for the development of immune-based
therapies in all subtypes of the disease.