Reduced number of CD169 ⁺ macrophages in pre‐metastatic regional lymph nodes is associated with subsequent metastatic disease in an animal model and with poor outcome in prostate cancer patients

Abstract

Background

Tumor‐derived antigens are captured by CD169 ⁺ (SIGLEC1 ⁺) sinus macrophages in regional lymph nodes (LNs), and are presented to effector cells inducing an anti‐tumor immune response. Reduced CD169 expression in pre‐metastatic regional LNs is associated with subsequent metastatic disease and a poor outcome in several tumor types, but if this is the case in prostate cancer has not been explored.

Methods

CD169 expression was measured with immunohistochemistry in metastasis‐free regional LNs from 109 prostate cancer patients treated with prostatectomy (January 1996 to April 2002). Possible associations of CD169 expression with PSA‐relapse, prostate cancer death, Gleason score, and other clinical data were assessed using Kaplan‐Meier survival‐ and Cox regression analysis. In addition, the Dunning rat prostate tumor model was used to examine CD169 expression in pre‐metastatic LNs draining either highly metastatic MatLyLu‐ or poorly metastatic AT1‐tumors.

Results

In patients with low CD169 immunostaining in metastasis‐free regional LNs, 8 of the 27 patients died from prostate cancer compared with only three of the 82 patients with high immunostaining ( P < 0.001). CD169 expression in regional LNs was not associated with PSA‐relapse. Rats with highly metastatic tumors had decreased CD169 immunoreactivity in pre‐metastatic regional LNs compared with rats with poorly metastatic tumors.

Conclusion

Low expression of CD169 in metastasis‐free regional LNs indicates a reduced anti‐tumor immune response. If verified in other studies, CD169 expression in regional LNs could, in combination with other factors, potentially be used as a marker of prostate cancer aggressiveness.