Abstract
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.
PI3K/AKT/mTOR and sonic hedgehog pathways cooperate together to inhibit human pancreatic cancer stem cell characteristics and tumor growth