Abstract
BACKGROUND: Programmed death-ligand 1 (PD-L1) plays important roles in the evasion of antitumor immunity. Because we observed the localization of PD-L1-positive (PD-L1(+)) cells in the marginal region of triple-negative breast cancer (TNBC) specimens, we hypothesized that the marginal microenvironment of TNBC would involve the induction of PD-L1(+) cells. METHODS: One hundred and one TNBC surgical specimens were examined. We performed immunohistochemical (IHC) studies of PD-L1, CD68, CD8, and pan-cytokeratin in these specimens. We analyzed the localization of IHC-positive cells and the distance between these cells by histological spatial analysis. RESULTS: In 30.7% of TNBC specimens, PD-L1(+) cells were located in the marginal region. Approximately three PD-L1(+) cells accumulated around a single TNBC cell. Most PD-L1(+) cells were located within 50 μm of TNBC cells. PD-L1(+) cells were indicated to interact with TNBC cells in the marginal region. PD-L1(+)CD68(+) cells were located in the marginal region, while CD68(+) macrophages (MΦs) were observed either in the marginal region or the core region. PD-L1 expression in MΦs was induced in the marginal region. The colocalization of CD8(+) T cells in the marginal region indicates that PD-L1 expression in MΦs would be induced by interaction with CD8(+) T cells. Because CD8(+) T cells are positive for CCL2, CCL2 may induce PD-L1 expression in MΦs. CONCLUSION: At the marginal microenvironment of TNBC, PD-L1 expression would be induced in MΦs by interaction with CD8(+) T cells through CCL2. The interaction between PD-L1(+) MΦs and TNBC cells would facilitate the growth of TNBC under antitumor immunity. These interactions would be potential targets for restoring antitumor immunity and suppressing TNBC progression.