Overexpression of PD-1 and CD39 in tumor-infiltrating lymphocytes compared with peripheral blood lymphocytes in triple-negative breast cancer

BACKGROUND AND AIM: Growing evidence highlighted the primary role of the immune system in the disease course of triple-negative breast cancer (TNBC). The study aim was to investigate the expression of PD-1 and CD39 on CD4(+) and CD8(+) cells infiltrating tumor tissue compared to their counterparts in peripheral blood and explore its association with tumor characteristics, disease progression, and prognosis in females with TNBC. PATIENTS AND METHODS: The study included 30 TNBC patients and 20 healthy controls. Cancer and normal breast tissue and peripheral blood samples were collected for evaluation of the expression of PD-1 and CD39 on CD4(+) and CD8(+)T cells by flow cytometry. RESULTS: A marked reduction in the percentage of CD8(+) T lymphocytes and a significant increase in the frequencies of CD4(+) T lymphocytes and CD4(+) and CD8(+) T lymphocytes expressing PD1 and CD39 were evident in tumor tissue in comparison with the normal breast tissue. The DFS was inversely related to the cancer tissue PD1(+)CD8(+) and CD39(+)CD8(+) T lymphocytes. Almost all studied cells were significantly increased in the tumor tissue than in peripheral blood. Positive correlations were detected among peripheral PD1(+)CD4(+)T lymphocytes and each of cancer tissue PD1(+)CD4(+), PD1(+)CD8(+)and CD39(+)CD8(+)T cells, and among peripheral and cancer tissue CD39(+)CD4(+)and CD39(+)CD8(+) T cells. CONCLUSIONS: The CD39 and PD1 inhibitory pathways are synergistically utilized by TNBC cells to evade host immune response causing poor survival. Hence, combinational immunotherapy blocking these pathways might be a promising treatment strategy in this type of cancer.