Implications for Immunotherapy of Breast Cancer by Understanding the Microenvironment of a Solid Tumor

SIMPLE SUMMARY: Breast cancer is one of the most common forms of cancer in women. Treatment options include immunotherapy where elements of the immune system are used directly or in a modified form. However, the surrounding ecosystem of a solid tumor forms a complex barrier of supportive and protective cells that needs to be penetrated to allow immunotherapies to be effective. A better understanding of the underlying mechanisms of the tumor microenvironment will help improve immunotherapies. This review will summarize the latest research concerning the tumor microenvironment of breast cancer and give implications for immunotherapy. ABSTRACT: Breast cancer is poorly immunogenic due to immunosuppressive mechanisms produced in part by the tumor microenvironment (TME). The TME is a peritumoral area containing significant quantities of (1) cancer-associated fibroblasts (CAF), (2) tumor-infiltrating lymphocytes (TIL) and (3) tumor-associated macrophages (TAM). This combination protects the tumor from effective immune responses. How these protective cell types are generated and how the changes in the developing tumor relate to these subsets is only partially understood. Immunotherapies targeting solid tumors have proven ineffective largely due to this protective TME barrier. Therefore, a better understanding of the interplay between the tumor, the tumor microenvironment and immune cells would both advance immunotherapeutic research and lead to more effective immunotherapies. This review will summarize the current understanding of the microenvironment of breast cancer giving implications for future immunotherapeutic strategies.