Abstract
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.
Highlights
In 2018, atezolizumab was approved to treat the triple negative breast cancer (TNBC) patients with PD-L1 expression [1]
CD155 is another immune checkpoint protein, expressing on tumor cells and interacts with CD96, CD226, and T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) on tumor-infiltrating lymphocytes to modulate the immune function in tumor immune microenvironment [6,7,8]
A total of 126 cases diagnosed with invasive BC were evaluated with CD155 expression, 38.1% (48) of the cases were stained as overexpression (Figure 1(a)), whereas 61.9% (78) were stained as low expression (Figure 1(b))
Summary
In 2018, atezolizumab was approved to treat the triple negative breast cancer (TNBC) patients with PD-L1 expression [1]. The percentage of BC patients who are eligible to received immune checkpoint inhibitor is less than. The immune checkpoint inhibitor targeting the PD1/PD-L1 pathway is limited for immunotherapy among BC patients. CD155 is another immune checkpoint protein, expressing on tumor cells and interacts with CD96, CD226, and T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) on tumor-infiltrating lymphocytes to modulate the immune function in tumor immune microenvironment [6,7,8]. Expression of CD155 was seldom reported to be related with the inhibitory immune function in tumor microenvironment of BC. We have investigated the expression of CD155 in BC tissues and the association with pathological characteristics, immune function of tumor microenvironment, and survival, in order to explore the immunotherapy potence of the CD155 pathway among BC patients
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call