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Purpose: The immune checkpoint inhibitor is approved for breast cancer treatment, but the low expression of PD-L1 limits the immunotherapy. CD155 is another immune checkpoint protein in cancers and interacts with ligands to regulate immune microenvironment. This study is aimed at investigating the expression of CD155 and the association with prognosis and pathological features of breast cancer., Methods: 126 patients were recruited this cohort study consecutively, and CD155 expression on tumor cells was detected by immunohistochemistry. The Kaplan-Meier survival curve and Cox hazard regression model were used to estimate the association., Results: 38.1% patients had an overexpression of CD155, and the proportion of tumor cells with CD155 overexpression was 17%, 39%, 37%, and 62% among Luminal A, Luminal B, HER2-positive, and triple negative breast cancer cases, respectively ( p < 0.05). Patients with CD155 overexpression had the Ki-67 index significantly higher than that of patients with low expression (42% vs. 26%). Though the number of tumor-infiltrating lymphocytes was higher among patients with CD155 overexpression (144/HPF vs. 95/HPF), the number of PD-1 + lymphocytes was significantly higher (52/HPF vs. 25/HPF, p < 0.05). Patients of CD155 overexpression had the disease-free and overall survival decreased by 13 months and 9 months, respectively ( p < 0.05). CD155 overexpression was associated with an increased relapse (HR = 13.93, 95% CI 2.82, 68.91) and death risk for breast cancer patients (HR = 5.47, 1.42, 20.99)., Conclusions: Overexpression of CD155 was correlated with more proliferative cancer cells and a dysfunctional immune microenvironment. CD155 overexpression introduced a worse relapse-free and overall survival and might be a potential immunotherapy target for breast cancer., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Yu-Chen Li et al.)

Objective: Breast cancer has become the most common cancer in women in China, and the clinicopathological features differ from those in Western patients. This study was performed to investigate the distribution of programmed cell death protein 1 (PD-1) + /PD-1 - tumor-infiltrating lymphocytes (TILs) and its association with clinicopathological features among Chinese patients with breast cancer., Methods: In total, 133 consecutive patients with primary breast cancer were recruited into this cross-sectional study from 2012 to 2013. TILs were measured by cell counts under high-power fields (HPFs). Immunohistochemistry was used to detect PD-1 expression on tumor-infiltrating lymphocytes in the microenvironment., Results: The median cell counts of the overall TILs, PD-1 + TILs, and PD-1 - TILs were 80, 18, and 55/HPF, respectively. The number of PD-1 - TILs was significantly lower in older than younger patients (50 vs. 60/HPF). Patients with positive E-cadherin expression had more PD-1 - TILs than patients with negative E-cadherin expression (57 vs. 27/HPF). The Ki-67 index was positively correlated with the cell counts of PD-1 + TILs, and the correlation coefficient was 0.29., Conclusions: PD-1 expression on TILs had different clinicopathological features in Chinese patients with breast cancer. E-Cadherin expression was associated with PD-1 - TILs; however, Ki-67 expression was associated with PD-1 + TILs.

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.