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

PLOS ONE(2022)

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摘要
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.
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