Distinct compartmental distribution of mature and immature dendritic cells in esophageal squamous cell carcinoma

Abstract

Dendritic cells (DCs) play a critical role in generating anti-tumor immunity. DC functional defect has been related to the growth and progression of various human cancers. In esophageal squamous cell carcinoma (ESCC), the examination of DCs using immunohistochemistry (IHC) with anti-S100 antibody has demonstrated an increased infiltration of DCs into the tumor mass, however, the distribution patterns of DCs at different maturation states in ESCC are not fully evaluated. In this study, we immunohistochemically analyzed the DC maturation status by examining the S100-positive DCs, CD1alpha-positive immature DCs (iDCs), and CD208-positive mature DCs (mDCs) and their distribution patterns in 45 ESCCs and 10 control tissues. The IHC analysis showed that the number of S100-positive DCs was increased in both the cancer epithelium and tumor stroma. Further phenotypic analyses revealed that intraepithelial DCs in the cancer mass were predominantly CD1alpha-positive iDCs. Whereas DCs presented in the tumor stroma were exclusively CD208-positive mDCs, CD208-positive mDCs were particularly dense in the margin of cancerous lesions and formed clusters with CD3-positive lymphocytes. The number of CD208-positive mDCs in the tumor mass was significantly lower than the number of CD1alpha-positive iDCs. The current results suggest that ESCC tissue comprises a high frequency of iDCs in the cancerous epithelium and a low density of mDCs in the tumor stroma. Such a distinct distribution pattern may reflect the ongoing DC tracking in ESCCs.