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Abstract
Objective This study aimed to investigate the correlation of CD4+/PD-1+ or CD4+/PD-1− tumor-infiltrating lymphocytes with pathological characteristics in breast cancer patients. Methods A cross-sectional study consecutively recruited 133 patients with invasive ductal breast cancer. The expression of CD4, programmed cell death protein 1 (PD-1), CK7, CK20, E-cadherin, or Ki-67 was detected by immunohistochemistry. The associations between CD4+/PD-1+ or CD4+/PD-1− tumor-infiltrating lymphocytes and pathological characteristics were evaluated. Results Elderly patients intended to have a lower level of CD4+/PD-1− tumor-infiltrating lymphocytes (p < 0.05). Patients with positive E-cadherin expression had higher median cell counts of CD4+/PD-1− tumor-infiltrating lymphocytes than patients with negative E-cadherin expression (30/HPF versus 10/HPF, p < 0.05). Counts of CD4+/PD-1+ tumor-infiltrating lymphocytes had a significant correlation with Ki-67 index that the correlation coefficient was 0.29 (p = 0.001). Positive CK20 expression was related to a higher level of CD4+/PD-1− tumor-infiltrating lymphocytes than negative CK20 expression (73/HPF versus 30/HPF, p < 0.05). Conclusion CD4+/PD-1+ or CD4+/PD-1− tumor-infiltrating lymphocytes showed diverse association with pathological features of breast cancer. CD4+/PD-1+ tumor-infiltrating lymphocytes had a significant relationship with Ki-67 expression whereas CD4+/PD-1− tumor-infiltrating lymphocytes had a significant relationship with E-cadherin expression. Further studies are warranted to explore the immunomodulatory effects of phenotypes of CD4+ T cell subsets in breast cancer.
Highlights
Breast cancer (BC) is the most common female cancer worldwide with 1.67 million new cases (25% of all incident cancer cases) in 2012 [1], and the mortality rate was higher in underdeveloped countries than in developed countries [1]
Programmed cell death protein 1 (PD-1), as an immune checkpoint expressed on T cells, binds to programmed cell death ligand 1 (PD-L1) on the surface of cancer cells and suppresses antitumor functions of T lymphocytes
We aimed to investigate the correlation of exhausted status of CD4+ helper T cells with pathological characteristics among BC patients
Summary
Breast cancer (BC) is the most common female cancer worldwide with 1.67 million new cases (25% of all incident cancer cases) in 2012 [1], and the mortality rate was higher in underdeveloped countries than in developed countries [1]. TILs are mainly composed of different subtypes of T cells, which play an important role in antitumor immunity. A high proportion of TILs predicted a favorable prognosis of BC patients [2]. The expression of PD-1 indicated exhausted function of lymphocytes and a high level of PD-1+ TILs correlated with a worse survival of BC [4]. The immune function of CD4+ T cells was affected by PD-1 expression. E-cadherin (E-Cad) and Ki-67 showed a significant relationship with BC prognosis [9]. These biomarkers were tested routinely in BC pathological diagnosis. We aimed to investigate the correlation of exhausted status of CD4+ helper T cells with pathological characteristics among BC patients
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