Immune cell composition and immunological profiles of the breast cancer microenvironment represented by histologically assessed tumor-infiltrating lymphocytes and PD-L1 expression: A systematic analysis

Abstract Background. A better understanding of tumor immunology can facilitate the development of new treatment strategies for various malignancies. Histologically assessed tumor-infiltrating lymphocytes (hTILs) and programmed cell death 1 ligand 1 (hPD-L1) have been established as prognostic or predictive biomarkers in certain subsets of breast cancer. However, the complexity of multiple types of immune cells is not fully understood. In this study, the immune cell fractions in breast cancer tissue and blood were evaluated to analyze their association with hTILs and hPD-L1. Methods. In total, 45 tumor and 18 blood samples were collected from breast cancer patients. The total leukocyte counts, proportions of 11 types of immune cells in the samples, and PD-L1 expression in each fraction were evaluated using multicolor flow cytometry for both the tumor and blood samples. The hTILs and hPD-L1 were evaluated with hematoxylin and eosin staining and immunohistochemistry respectively. Results. The immune cell composition of the blood showed a partial correlation with that of the tumor tissue; however, no significant association was found between the blood immune cell compositions and hTIL or hPD-L1 expression. A higher hTIL was associated with increased leukocyte infiltration as well as a higher proportion of CD4+ and CD8+ T cells and lower proportion of natural killer cells and natural killer T cells. PD-L1 was highly expressed in the monocyte/macrophage (Mo/Mφ), nonclassical monocyte (CD16+ Mo), myeloid-derived suppressor cell (MDSC), dendritic cell (DC), and myeloid dendritic cell (mDC) fractions in the tumor tissues. hPD-L1 positivity was associated with increased leukocyte infiltration in the tumor tissues and PD-L1 expression in Mo/Mφ, CD16+ Mo, MDSC, DC, and mDC fractions. Conclusion. There was a partial correlation in the composition of immune cells at the tumor site and that in the peripheral blood. A high proportion of hTILs reflects not only higher immune cell infiltration but also differences in the immune responses in the tumor microenvironment. Non-B-cell antigen-presenting cell fractions such as Mo/Mφ, CD16+ Mo, MDSC, DC, and mDC fractions are involved primarily in the PD-L1 pathway in the breast cancer microenvironments.