Abstract
CD169 (sialoadhesin) is a sialic acid receptor that is expressed on specific macrophages such as lymph node sinus macrophages. Animal studies have suggested that CD169(+) macrophages have a pro-inflammatory property, however, the role of these cells in human diseases has not been clarified. In our in vitro experiments with human macrophages, pro-inflammatory cytokines, such as type 1 interferon, induced strong expression of CD169, suggesting that CD169 might be a specific marker of inflammatory macrophages. To examine the role of CD169 in antitumor immunity, we examined the expression of CD169 in regional lymph nodes (RLNs) and its association with overall survival in colorectal carcinoma (CRC). In a clinicopathological analysis on 83 CRC patients, paraffin-embedded specimens were evaluated for CD169 expression of RLN macrophages by immunohistochemistry. We found, for the first time, a high density of CD169(+) macrophages was significantly associated with longer overall survival; multivariate analysis showed that the ratio of CD169(+) cells to CD68(+) cells was an independent prognostic factor. The majority of CD169(+) macrophages were in direct contact with CD8(+) T cells expressing CD43, a major ligand of CD169. We also found that the density of CD169(+) macrophages had a positive correlation with the number of CD8(+) cytotoxic T cells infiltrating tumor tissues. These data suggest that CD169(+) macrophages in RLNs promote CD8(+) T-cell-mediated antitumor immunity and are associated with a better prognosis for CRC patients. CD169(+) macrophages in RLNs could be a useful marker for assessing clinical prognosis and monitoring antitumor immunity in patients with CRC.