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. 2022 Jan 20;17(1):e0262650.
doi: 10.1371/journal.pone.0262650. eCollection 2022.

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

Asmaa M Zahran  1 , Amal Rayan  2 , Zeinab Albadry M Zahran  3 , Wael M Y Mohamed  4   5 , Dalia O Mohamed  6 , Mona H Abdel-Rahim  7 , Omnia El-Badawy  7
Affiliations

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

Asmaa M Zahran et al. PLoS One. .

Abstract

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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Conflict of interest statement

the authors have declared that no competing interests exist

Figures

Fig 1
Fig 1. Flow cytometric analysis of CD39 and PD1 expression by the T Lymphocyte subsets.
A: The lymphocyte population was gated from peripheral blood mononuclear cells by drawing (R1) based on the forward/side scatter characteristics. B, C: CD3 expression was analysed on the gated lymphocytes, and the CD3+ cells were selected by (R2) for further analysis based on CD4 and CD8 expression. (R3) and (R4) represent the regions used to choose the CD4+ andCD8+T cells, respectively. D-H: Dot plots representing CD39 and PD1 expression by CD4+ andCD8+ T cells.
Fig 2
Fig 2. Disease-free survival (DFS) among 30 patients with triple-negative breast cancer (TNBC).
Fig 3
Fig 3. DFS association with tumor-infiltrating (A) PD1+CD8+ T lymphocytes (p = 0.007), and (B) CD39+CD8+ T lymphocytes (p = 0.03), in 30 TNBC patients.
Fig 4
Fig 4. Differences in the mean percentages of tumor-infiltrating PD1+CD4+ T lymphocytes according to local recurrence (p = 0.03) for the 30 patients with TNBC (Independent t-test).
Fig 5
Fig 5. Correlation of peripheral PD1+CD8+ T lymphocytes with DFS in 30 TNBC patients (p = 0.04).
Fig 6
Fig 6. Significant differences in the mean percentages of PD1+CD8+ (p = 0.03) and CD39+CD8+ peripheral T lymphocytes (p = 0.04) according to pathologic type (ILC, and IDC respectively), in 30 patients with TNBC (Independent t-test).
Fig 7
Fig 7. Forest plot of HR for different lymphocyte subsets.
See this image and copyright information in PMC

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