Hana Triki1, Slim Charfi2, Lobna Bouzidi2, Wala Ben Kridis3, Jamel Daoud4, Kais Chaabane5, Tahia Sellami-Boudawara2, Ahmed Rebai1, Boutheina Cherif6. 1. Laboratory of Molecular and Cellular Screening Processes, Centre de Biotechnologie de Sfax, Sfax, Tunisia. 2. Department of Pathology, University Hospital Habib Bourguiba, Sfax, Tunisia. 3. Department of Medical Oncology, University Hospital Habib Bourguiba, Sfax, Tunisia. 4. Department of Radiotherapy, University Hospital Habib Bourguiba, Sfax, Tunisia. 5. Department of Gynecology, University Hospital Hédi Chaker, Sfax, Tunisia. 6. Laboratory of Molecular and Cellular Screening Processes, Centre de Biotechnologie de Sfax, Sfax, Tunisia. Electronic address: boutheina.cherif.cbs@gmail.com.
Abstract
AIMS: CD155 is a ligand of the NK activating receptor DNAM-1, it has been described in a variety of human malignancies, but its expression in breast cancer remains unclear and poorly studied. MAIN METHODS: CD155 expression and NK cells infiltration were investigated in 158 patients with breast cancer by immunohistochemistry (IHC). Statistical analyses were performed to evaluate correlations of CD155 expression with clinical-pathological features, prognosis and tumor immunity. KEY FINDINGS: Tumor cytoplasmic CD155 (cyt-CD155) was associated with lymphovascular invasion (p = 0.011), and membranous CD155 (m-CD155) was strongly correlated with the presence of Tumor Infiltrating natural killer cells (NK-TILs) (p = 0.0003). Survival analysis demonstrated that patients with high cyt-CD155 had a significantly worse overall survival (p < 0.001) and death free survival (p = 0.014) than those with low expression, while high levels of m-CD155 correlated with a better prognosis (p = 0.037). Furthermore, we found that patients with m-CD155Low/NKLow tumors had a significantly reduced overall survival (p = 0.012). Multivariate analysis showed that positive tumor m-CD155 status was a significant independent marker of good prognosis. Meanwhile, high cyt-CD155 expression was identified as an independent poor prognostic predictor, suggesting a key role in this malignancy. SIGNIFICANCE: Altogether, our results revealed that cyt-CD155 was associated with invasiveness and poorer prognosis, but the concomitant presence of m-CD155 and NK-TILs had an opposite prognostic relevance in breast cancer. These results raised the importance of CD155 IHC analysis to elucidate biomarker localization, leading to better understand and design therapeutic molecule targeting CD155 in breast tumors.
AIMS: CD155 is a ligand of the NK activating receptor DNAM-1, it has been described in a variety of humanmalignancies, but its expression in breast cancer remains unclear and poorly studied. MAIN METHODS:CD155 expression and NK cells infiltration were investigated in 158 patients with breast cancer by immunohistochemistry (IHC). Statistical analyses were performed to evaluate correlations of CD155 expression with clinical-pathological features, prognosis and tumor immunity. KEY FINDINGS:Tumor cytoplasmic CD155 (cyt-CD155) was associated with lymphovascular invasion (p = 0.011), and membranous CD155 (m-CD155) was strongly correlated with the presence of Tumor Infiltrating natural killer cells (NK-TILs) (p = 0.0003). Survival analysis demonstrated that patients with high cyt-CD155 had a significantly worse overall survival (p < 0.001) and death free survival (p = 0.014) than those with low expression, while high levels of m-CD155 correlated with a better prognosis (p = 0.037). Furthermore, we found that patients with m-CD155Low/NKLow tumors had a significantly reduced overall survival (p = 0.012). Multivariate analysis showed that positive tumor m-CD155 status was a significant independent marker of good prognosis. Meanwhile, high cyt-CD155 expression was identified as an independent poor prognostic predictor, suggesting a key role in this malignancy. SIGNIFICANCE: Altogether, our results revealed that cyt-CD155 was associated with invasiveness and poorer prognosis, but the concomitant presence of m-CD155 and NK-TILs had an opposite prognostic relevance in breast cancer. These results raised the importance of CD155 IHC analysis to elucidate biomarker localization, leading to better understand and design therapeutic molecule targeting CD155 in breast tumors.
Authors: Carlos E Sanchez; Ehsan P Dowlati; Ashley E Geiger; Kajal Chaudhry; Matthew A Tovar; Catherine M Bollard; Conrad Russell Y Cruz Journal: Transplant Cell Ther Date: 2020-09-29