The Role of Immune Cells in Breast Tissue and Immunotherapy for the Treatment of Breast Cancer

Abstract

Immune cells are present in normal breast tissue and in breast carcinoma. The nature and distribution of the immune cell subtypes in these tissues are reviewed to promote a better understanding of their important role in breast cancer prevention and treatment. We conducted a review of the literature to define the type, location, distribution, and role of immune cells in normal breast tissue and in in situ and invasive breast cancer. Immune cells in normal breast tissue are located predominantly within the epithelial component in breast ductal lobules. Immune cell subtypes representing innate immunity (NK, CD68⁺, and CD11c⁺ cells) and adaptive immunity (most commonly CD8⁺, but CD4⁺ and CD20⁺ as well) are present; CD8⁺ cells are the most common subtype and are primarily effector memory cells. Immune cells may recognize neoantigens and endogenous and exogenous ligands and may serve in chronic inflammation and immunosurveillance. Progression to breast cancer is characterized by increased immune cell infiltrates in tumor parenchyma and stroma, including CD4⁺ and CD8⁺ granzyme B⁺ cytotoxic T cells, B cells, macrophages and dendritic cells. Tumor-infiltrating lymphocytes in breast cancer may serve as prognostic indicators for response to chemotherapy and for survival. Experimental strategies of adoptive transfer of breast tumor-infiltrating lymphocyte may allow regression of metastatic breast cancer and encourage development of innovative T-cell strategies for the immunotherapy of breast cancer. In conclusion, immune cells in breast tissues play an important role throughout breast carcinogenesis. An understanding of these roles has important implications for the prevention and the treatment of breast cancer.

Keywords: Breast ductal cells; Immunology; Intraepithelial lymphocytes; Tumor immunology; Tumor-infiltrating lymphocytes.

Fig.1. The nature and distribution of immune cells in normal breast tissue.

A variety of immune cells are present in normal breast tissue, including both lymphocytes and myeloid-derived cells. Immune cells are located primarily within the ductal epithelium (intraepithelial) but may be present in the stroma as well (not depicted). The stromal extracellular matrix (ECM) also contains a variety of cell types and structures which may interact with immune cells and the epithelium (adapted from Degnim et al).

Fig 2.. Immune cells in breast proliferative disease and breast cancer.

Immune Cells, including CD68+(Macrophages/Monocytes),CD3+ (CD4+, CD8+), and Cytotoxic Lymphocytes (CTL) are Present in Breast Proliferative Disease and Increase in the Parenchyma and Stroma With Progression to Breast Cancer. Relative Increases for Each Cell Type, With Benign Proliferation as a Baseline, are Shown on a Logarithmic Scale in the Graphs Below the Figure. (Adapted from Data from within Hussein and Hassan)