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Biology subjects

Haga, H.

Publications and source records attributed to Haga, H..

2 recordsLinked to original sources

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.

cancer biology↗

Conversion of cancer-associated fibroblasts from pro- to antitumor improves the sensitivity of pancreatic cancer to chemotherapeutics

Previous therapeutic attempts to deplete cancer-associated fibroblasts (CAFs) or inhibit their proliferation in pancreatic ductal adenocarcinoma (PDAC) were not successful in mice or patients. Thus, CAFs may be tumor suppressive or heterogeneous, with distinct cancer-restraining and -promoting CAFs (rCAFs and pCAFs, respectively). Here, we show that induced expression of the glycosylphosphatidylinositol-anchored protein Meflin, a rCAF-specific marker, in CAFs by genetic and pharmacological approaches improved the chemosensitivity of mouse PDAC. A chemical library screen identified Am80, a synthetic, non-natural retinoid, as a reagent that effectively induced Meflin expression in CAFs. Am80 administration improved the sensitivity of PDAC to chemotherapeutics, accompanied by increases in tumor vessel area and intratumoral drug delivery. Mechanistically, Meflin was involved in the suppression of tissue stiffening by interacting with lysyl oxidase to inhibit its collagen crosslinking activity. These data suggested that modulation of CAF heterogeneity may represent a strategy for PDAC treatment.

cancer biology↗