Background CD200, a negative T cell regulator as well as a cancer stem cell marker, is a significant prognostic factor and potential therapeutic target in specific cancers. However, the clinical significance of CD200 is unknown in pancreatic ductal adenocarcinoma (PDAC). Methods CD200 was evaluated in 220 resected PDAC patients. Surgery was performed with or without neoadjuvant chemotherapy (NACRT), and adjuvant therapy was administered with systemic therapy or systemic therapy added with hepatic arterial infusion (HAI) therapy. We investigated the clinicopathological outcomes associated with CD200, in relation to the administered multimodal treatment. We further evaluated the impact of the immunological and cancer stem cell properties associated with CD200. Results NACRT patients had a lower average age, lower lymph node metastasis, higher negative surgical margins, and higher HAI administration rate, compared to upfront surgery (US) patients. NACRT was associated with better OS, and higher CD200 expression (66.4% vs. 32.2%, P<0.001) compared to US. CD200 was an independent poor prognostic factor in NACRT (hazard ratio 2.51; 95% confidence interval 1.35-4.66; P = 0.004), but not in US patients. In NACRT patients, the hepatic recurrence rate was relatively high in CD200+ cases despite HAI therapy. CD200 was associated with significantly lower CD4+, CD8+, and CD45RO+ tumor-infiltrating lymphocyte levels. Furthermore, the correlation of CD200 with pancreatic cancer stem cell markers CD44/CD24/ESA was stronger in irradiated human pancreatic cancer cells. Conclusions Our data highlight novel roles for CD200 in immune evasion as well as therapy resistance in pancreatic cancer.

BackgroundAberrant expression of CD70 in several malignancies is potentially associated with poor patient prognosis and could serve as a therapeutic target. However, the clinical relevance of CD70 expression in pancreatic cancer has not been thoroughly explored.MethodsWe evaluated CD70 expression in 166 surgical specimens obtained from human patients with pancreatic cancer. We analyzed the function of CD70 in proliferation and migration using pancreatic cancer cell lines with silenced CD70 expression.ResultsCD70 expression was positively stained in 42 patients (25%). In the whole cohort, high CD70 expression was not associated with overall survival (OS: 33.1 vs. 40.8 months, P = 0.256), although it was significantly associated with inferior OS in a population of patients that completed adjuvant chemotherapy (P = 0.027). Moreover, the incidence of hematogenous metastasis was significantly higher in patients with high CD70 expression than in those with low CD70 expression (P = 0.020). This finding was also statistically significant in multivariate analyses (P = 0.001). In vitro experiments demonstrated that CD70 expression contributed to cancer cell proliferation independently of gemcitabine treatment as well as cell migration. Furthermore, real-time polymerase chain reaction analysis of frozen surgical tissues showed a correlation between the expression of CD70 and mesenchymal markers.ConclusionsCD70 expression in pancreatic cancer might be involved in hematogenous metastasis. Furthermore, our results imply that CD70 overexpression can serve as a novel prognostic factor and a potential therapeutic target in patients who have completed adjuvant chemotherapy.