Aging potentially reduces CD169 expression in sinus macrophages of pelvic lymph nodes
Yuki Ibe1,2, Yojiro Ozaki1,2, Toshiki Anami1,2
1Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1, Honjo, Kumamoto Chuo-Ku, Kumamoto, 860-8556, Japan.
Abstract:
The number of patients with prostate cancer has been increasing around the world. Although anticancer immunotherapy targeting the immune checkpoint molecules has been approved for many types of cancer, no significant anti-cancer effects have been observed in patients with prostate cancer. Lymph node sinus macrophages (LSMs) are known to work as antigen-presenting cells, which are critical for anticancer immune responses. Previous studies have suggested that CD169 expression in LSMs affects anticancer immune responses in several cancers, including prostate cancer. In the present study, we aimed to examine the correlation between the tumor immune microenvironment and activation status of LSMs in patients with prostate cancer. Forty-two cases of high-risk localized prostate cancer treated using robot-assisted laparoscopic radical prostatectomy and lymph node dissection between 2017 and 2021 were enrolled. CD169 expression in LSMs was examined by immunohistochemistry. The results indicated that CD169 expression in LSMs was significantly decreased in older (≥ 75 years) compared with younger patients. However, no significant correlation was found between CD169 expression and any other clinicopathological factors. In addition, CD3- and CD8-postitive lymphocytes in primary cancer tissues were evaluated in the same cases, and their correlations with CD169 expression in LSMs were tested. Although these lymphocytes tended to be higher in CD169high than in CD169low cases, the difference was not statistically significant. In conclusion, we found that CD169 expression was upregulated in older patients and tended to be related to T cell infiltration in cancer tissues. Therefore, the downregulation of CD169 in LSMs might be involved in the reduced anticancer immune response in prostate cancer.
Insights
CD169 expression on lymph node sinus macrophages is reduced in older prostate cancer patients. This downregulation may impair the anticancer immune response, highlighting a potential target for improving immunotherapy in prostate cancer.
Area of Science:
- Oncology
- Immunology
- Pathology
Background:
- Prostate cancer incidence is rising globally.
- Current immunotherapies show limited efficacy in prostate cancer.
- Lymph node sinus macrophages (LSMs) are crucial antigen-presenting cells for anti-cancer immunity.
- CD169 expression on LSMs is implicated in anti-cancer responses in various cancers, including prostate cancer.
Purpose of the Study:
- To investigate the relationship between the tumor immune microenvironment and LSM activation status in prostate cancer patients.
- To analyze CD169 expression in LSMs and its correlation with clinicopathological factors and immune cell infiltration.
Main Methods:
- Retrospective analysis of 42 high-risk localized prostate cancer cases treated with robot-assisted radical prostatectomy and lymph node dissection.
- Immunohistochemistry was used to assess CD169 expression in LSMs.
- Evaluation of CD3 and CD8 positive lymphocytes in primary tumor tissues.
Main Results:
- CD169 expression in LSMs was significantly lower in older patients (≥ 75 years) compared to younger patients.
- No significant correlation was observed between CD169 expression and other clinicopathological factors.
- While CD3 and CD8 positive lymphocytes tended to be higher in CD169-high cases, this difference was not statistically significant.
Conclusions:
- CD169 expression in LSMs is reduced in older prostate cancer patients.
- The observed downregulation of CD169 may contribute to diminished anti-cancer immune responses in prostate cancer.
- CD169 expression warrants further investigation as a potential factor influencing immunotherapy outcomes in prostate cancer.
