Clinical significance of CD155 expression and correlation with immune cell infiltration in triple-negative breast cancer

As a newly focused immune checkpoint protein in cancers, CD155 is a potential target in immunotherapy. Tumor microenvironment (TME) as a crucial regulatory factor in immunotherapy, also plays a significant role in the development and progression of triple-negative breast cancer (TNBC). This study aims to further clarify the relationship between the expression of CD155 and TME in TNBC.

We conducted a retrospective analysis of 182 patients with TNBC who underwent surgical treatment at The First Affiliated Hospital of Bengbu Medical University between January 2014 and December 2018. CD155, stromal tumor-infiltrating lymphocytes (sTILs), CD4, CD8, and CD163 expression levels in TNBC specimens were assessed by immunohistochemistry. We analyzed the expression of CD155, the degree of sTIL infiltration, the profiles of immune cell subsets, and their associations with clinicopathological characteristics and survival outcomes. At the same time, the relationship between CD155 expression, TNBC progression, and immune cell infiltration in the TME was evaluated using both the clinical samples and public datasets.

Among the 182 TNBC patients, 131 (72.0%) were CD155 high expression, and 51 (28.0%) were CD155 low expression. CD155 expression was positively correlated with tumor diameter, lymph node metastasis, and Ki-67 status (all P<0.05). There were 112 patients (61.5%) with sTILs low infiltration and 70 patients (38.5%) with sTILs high infiltration. One hundred and twelve (61.5%) were identified with sTIL slow infiltration and 70 (38.5%) with sTILs high infiltration, sTILs were negatively correlated with lymph node metastasis (r_s =-0.189, P=0.01) and positively correlated with Ki-67 status (r_s =0.390, P<0.001). CD8⁺sTILs were negatively correlated with lymph node metastasis (r_s =-0.240, P=0.001) and positively correlated with Ki-67 status (r_s =0.367, P<0.001). CD4⁺sTILs were negatively correlated with lymph node metastases (r_s =-0.184, P=0.01). CD163⁺sTILs were positively correlated with histological grade (r_s =0.164, P=0.03) and Ki-67 status (r_s =0.147, P=0.048). Spearman correlation analysis showed that CD155 expression level was positively correlated with CD163 expression level in TME (P<0.05). Univariate analysis showed that tumor size, histological grade, lymph node metastasis, sTILs content, CD8, CD4, CD163, and CD155 were correlated with disease-free survival (DFS) and overall survival (OS) (all P<0.05). DFS and OS. Multivariate analysis showed that tumor size, lymph node metastasis, CD8, CD163 and CD155 had significant effects on DFS (P<0.05), and lymph node metastasis, CD8, CD163 and CD155 had significant effects on OS (P<0.05). Kaplan-Meier survival curve showed that there were significant differences in DFS and OS among patients with high or low expression of CD8, CD4, CD163, sTILs, and CD155 (all P<0.05).

Overexpression of CD155 may contribute to the formation of the immunosuppressive TME mediated by M2 macrophages. CD155 overexpression introduced a worse relapse-free survival and OS and might be a potential immunotherapy target in TNBC patients.