Expression of PD-1 on CD4(+) Tumor-Infiltrating Lymphocytes in Tumor Microenvironment Associated with Pathological Characteristics of Breast Cancer

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.