CD169‐positive macrophages in regional lymph nodes are associated with a favorable prognosis in patients with colorectal carcinoma

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

Natural compounds that regulate lymph node sinus macrophages: Inducing an anti-tumor effect by regulating macrophage activation

“…Type I interferon, such as IFN-α, is known to induce CD169 expression in macrophages, 19 and we initially confirmed that IFN-α enhanced CD169 expression in HMDMs (Fig. 1B).…”

“…19 Patients with a higher density of CD169-positive macrophages showed a significantly better overall survival than those with a lower density. 19 These observations suggested that elevated CD169 expression in sinus macrophages was closely associated with the induction of anti-tumor immune responses and exerted a beneficial effect on the clinical course. 19 Similar observations were subsequently observed in patients with melanoma, endometrial cancer, and breast cancer.…”

“…19 These observations suggested that elevated CD169 expression in sinus macrophages was closely associated with the induction of anti-tumor immune responses and exerted a beneficial effect on the clinical course. 19 Similar observations were subsequently observed in patients with melanoma, endometrial cancer, and breast cancer. [25][26][27][28] A number of methods for targeting antigens to LN macrophages have been investigated as part of the ongoing development of lymphatic-targeted vaccines.…”

CD169 identifies an activated CD8+T cell subset in regional lymph nodes that predicts favorable prognosis in colorectal cancer patients

“…Consistent with previous reports, CD169 protein was mainly expressed on CD68 C Mf in the LN sinus. 27,35 Interestingly, multi-staining confocal microscopy analysis revealed a certain proportion of CD169 C cells were CD3 C CD8 C T cells (Fig. 1A and S2).…”

“…[21][22][23][24][25] A recent study demonstrated that CD169 C Mf could effectively generate CTL responses by cross-priming CD8 C T cells, which in turn, conferred immunity against re-exposure to the malignant cells. 26 The expression of CD169 in tumor-draining LN and its association with survival in CRC patients has been recently reported 27 ; however, the specific composition and function of CD169 C cells in tumor-draining LNs of cancer patients remain largely unknown. In the current study, we addressed this issue in CRC and identified a novel T cell subset, CD169 C CD8 C T cells.…”