Background. Many tumor infiltrating lymphocytes (TILs) are T-regulatory cells that promote immune tolerance by via IL-10 acting on IL-10 receptor-alpha (IL-10R) on macrophages. Pro-inflammatory M1 macrophages inhibit tumor growth while anti-inflammatory M2 macrophages enhance tumor growth and metastasis, as demonstrated in pancreas, colon, liver, and lung cancer. CD206+ M2 macrophages recruit fibroblasts after tissue insult. Programmed death 1 (PD-1) protein is a cell membrane receptor expressed by T-cells, natural killer cells, and B-cells. Binding to ligands PD-L1 and PD-L2 inhibits T-cell activation and enhances regulatory function to decrease immune response.
Design. We examined IL-10R expression in axillary lymph nodes of 15 patients with breast ductal adenocarcinoma. Twelve had at least one lymph node positive for metastatic carcinoma. Tissue microarrays (TMAs) including metastatic tumor cells and lymphoid tissue were stained for IL-10R (NBP2-46046), PD-L1 (clone 28-8), CD4, CD8, and CD206 (clone15-2).
Results. IL-10R was expressed on peri-tumoral and sinusoidal macrophages also positive for CD206 and PD-L1. Macrophages in cases without metastases were also triple positive for IL-10R, CD206, and PD-L1. TILs were positive for IL-10R, the majority co-expressing CD4.
Conclusion. The presence of IL-10R and PD-L1 on the CD206+ macrophages along with IL-10R on the CD4+ T-cells in lymph nodes of patients with breast carcinoma suggests an environment that induces T-cells dysfunction and anergy. PD-1 expression was restricted on the lymphocyte within the germinal center and no PD-1 expression was noted on the TILs. These data support the use of immunotherapy to boost the immune function in breast carcinoma.
Texas Tech University Health Sciences Center El Paso Department of Pathology