Abstract 1352: Extracellular adenosine suppress CD8+ T cell attraction resulting in poor prognosis in pancreatic ductal adenocarcinoma

Abstract Background: CD73 is a cell surface enzyme. Extracellular ATP and ADP are converted to AMP catalyzed by CD39, then AMP is converted to adenosine by CD73 in the tumor microenvironment (TME). Accumulating extracellular adenosine is known to play an immune suppressive role in TME of various cancers, however, its role in pancreatic ductal adenocarcinoma (PDAC) remains elusive. This study aimed to explore the role of CD73 in PDAC. Methods: To examine CD73 role in PDAC, we used both bioinformatical and experimental approaches. We employed a publicly available dataset, The Cancer Genome Atlas (TCGA) to analyze clinical relevance by bioinformatic approaches. In order to confirm the findings and explore the mechanisms from the bioinformatical analyses, we conducted in vitro, in vivo experiments. Murine PDAC cell line, Panc02 was used together with overexpression technique. Results: We found that high expression of CD73 was significantly associated with poor disease-free survival (P<0.001) and overall survival (P=0.002) in PDAC patients of TCGA cohort. Multivariate analyses revealed that CD73 was an independent prognostic factor in both disease-free (P=0.001) and overall survival (P=0.005). A deconvolution algorism, xCell showed that the CD73 high expression tumor showed less CD8+ T cell infiltration compared to the counterpart in TCGA cohort (P=0.009). There was no significant survival difference between the control and CD73 overexpressing PDAC cell bearing mice of carcinomatosis model when the experiment was conducted in immune deficient mice. On the other hand, when we implanted the cells into immune competent mice, CD73 overexpressing tumor showed significantly shorter survival (P<0.001). Further, the CD73 overexpressing tumor had less CD8+ T cell infiltration compared to the control mice (P=0.041). Co-culture experiments revealed that CD8+ T cell proliferation was suppressed when they were cultured with CD73 overexpression PDAC cells (P=0.011). Conclusion: We found that high expression of CD73 was associated with poor prognosis along with less CD8+ T cell infiltration in PDAC. These results suggest that accumulated adenosine in the TME suppressed CD8+ T cell infiltration in CD73 high expression tumor. Citation Format: Eriko Katsuta, Yasushi Ichikawa, Kazuaki Takabe, Subhamoy Dasgupta, Daisuke Ban. Extracellular adenosine suppress CD8+ T cell attraction resulting in poor prognosis in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1352.