MP18-09 ROLE FOR THE ECTONUCLEOTIDASE CD39

Abstract

INTRODUCTION AND OBJECTIVE: Extracellular adenosine generates a highly immunosuppressive microenvironment in solid tumors. The ectonucleotidases, CD39 and CD73, are important factors in adenosine production, highlighting a future target for immune-checkpoint mediators and anti-tumorgenesis. Herein, we reveal a comprehensive CD39/CD73 expression and outcome using clear cell renal cell carcinoma (ccRCC) specimens across primary and metastatic lesions. METHODS: We examined 152 ccRCC tissue samples, in which 105 were from primary lesions and 47 from metastases. The cell-by-cell CD39/CD73 expression analysis was immunohistochemically conducted by the virtual slide scanner and automatic single-cell count system. We further counted immune-labelled CD8, PD-1, and PD-L1 positive cells in ccRCC tumors and clarified a relationship between cancer immunity and adenosine signaling. RESULTS: We defined the median values of CD39/CD73-positive cell number in primary lesions as the cut-off for high-/low-CD39/CD73 expression. In 105 cases of primary ccRCC, high-CD39 expression was significantly associated with tumor recurrence during the median follow-up period of 99 months (p=0.015, Fig.1). However, no significant difference was noted by CD73 expression in ccRCC prognosis (p=0.912). Assessing cancer immunity and adenosine signaling revealed that CD39 expression correlated with PD-1 expression not only in primary ccRCC (r=0.525, p<0.001) but tumor metastases (r=0.464, p=0.001). Further, CD39 expression in metastases correlated with PD-L1 expression (r=0.525, p<0.001). New prognostic classification model combined with CD39 and PD-1 expression could depict a subgroup with poor prognosis from high-CD39 balk population in ccRCC (p=0.021, Fig.2). CONCLUSIONS: Ectonucleotidase CD39 expression levels may be a new biomarker for ccRCC prognosis. Further, for the first time we reveal a relationship between cancer immunity and adenosine signaling in ccRCC, promoting a rational combination immunotherapy strategy in future clinical practice.Source of Funding: None.