Selective elimination of CD169+ macrophages in lymph nodes invaded by breast cancers

Breast cancer cells suppress the host immune system to efficiently invade the lymph nodes; however, the underlying mechanism remains incompletely understood. Here, we report that metastasized breast cancer cells selectively eliminate CD169+ lymph node sinus macrophages, an initiator of anti-cancer immunity, from the lymph nodes. The comparison between paired lymph nodes with and without metastasis from the same patients demonstrated that the number of CD169+ macrophages was reduced in metastatic lymph nodes, whereas the numbers of other major immune cell types were unaltered. We also detected the infiltration of CD169+ macrophages into metastasized cancer tissues depending on sections, suggesting that CD169+ macrophages were gradually eliminated after anti-cancer reactions. Furthermore, CD169+ macrophage elimination was prevalent in major breast cancer subtypes and correlated with breast cancer staging. Collectively, we propose that metastasized breast cancer cells dispel CD169+ macrophages from lymph nodes in a phased manner, disabling a critical step of anti-cancer immunity. ### Competing Interest Statement KK: grants from TERUMO, Astellas, Eli Lilly, Kyoto Breast Cancer Research Network; consulting fee from Becton Dickinson Japan; honoraria from Eisai, Chugai, and Takeda; MT: grants from Chugai, Takeda, Pfizer, Taiho, JBCRG Assoc., KBCRN Assoc., Eisai, Eli Lilly, Daiichi-Sankyo, AstraZeneca, Astellas, Shimadzu, Yakult, Nippon Kayaku, AFI Technology, Luxonus, Shionogi, GL Science, and Sanwa Shurui; honoraria from Chugai, Takeda, Pfizer, Kyowa-Kirin, Taiho, Eisai, Daiichi-Sankyo, AstraZeneca, Eli Lilly, MSD, Exact Science, Novartis, Shimadzu, Yakult, Nippon Kayaku, Devicore Medical Japan, Sysmex; Advisory Board of Daiichi-Sankyo, Eli Lilly, BMS, Athenex Oncology, Bertis, Terumo, Kansai Medical Net; Board of Directors of JBCRG Assoc., KBCRN, NPO org. OOTR, and JBCS Assoc; Associate Editor of the British Journal of Cancer, Scientific Reports, Breast Cancer Research and Treatment, Cancer Science, Frontiers in Women's Cancer, Asian Journal of Surgery, Asian Journal of Breast Surgery. All remaining authors declare no conflicts of interest.