美国爱因斯坦医学院Julio A. Aguirre-Ghiso小组发现，肺驻留肺泡巨噬细胞调节乳腺癌转移的时机。相关论文于2024年10月7日在线发表在《细胞》杂志上。

研究人员表明，组织驻留的肺泡巨噬细胞通过诱导休眠来抑制乳腺癌在肺泡中的转移。通过配体-受体定位和活体成像发现，肺泡巨噬细胞表达转化生长因子（TGF）-β2。这种表达以及通过TGF-βRIII受体与癌细胞的持续相互作用使癌细胞保持在休眠状态。

去除肺泡巨噬细胞或在癌细胞中失去TGF-β2受体会触发转移觉醒。侵袭性乳腺癌细胞要么被肺泡巨噬细胞抑制，要么通过避免相互作用和下调TGF-β2受体来逃避这种抑制。在侵袭性细胞中恢复TGF-βRIII，会重新建立TGF-β2介导的巨噬细胞生长抑制。

因此，肺泡巨噬细胞作为转移免疫屏障，而TGF-β2信号的下调使癌细胞能够克服巨噬细胞介导的生长抑制。

据介绍，乳腺转移癌细胞（DCC）可以在肺部保持休眠状态很长时间，但限制它们扩展的机制尚不清楚。

附：英文原文

Title: Lung-resident alveolar macrophages regulate the timing of breast cancer metastasis

Author: Erica Dalla, Michael Papanicolaou, Matthew D. Park, Nicole Barth, Rui Hou, Deisy Segura-Villalobos, Luis Valencia Salazar, Dan Sun, Alistair R.R. Forrest, Maria Casanova-Acebes, David Entenberg, Miriam Merad, Julio A. Aguirre-Ghiso

Issue&Volume: 2024-10-07

Abstract: Breast disseminated cancer cells (DCCs) can remain dormant in the lungs for extended periods, but the mechanisms limiting their expansion are not well understood. Research indicates that tissue-resident alveolar macrophages suppress breast cancer metastasis in lung alveoli by inducing dormancy. Through ligand-receptor mapping and intravital imaging, it was found that alveolar macrophages express transforming growth factor (TGF)-β2. This expression, along with persistent macrophage-cancer cell interactions via the TGF-βRIII receptor, maintains cancer cells in a dormant state. Depleting alveolar macrophages or losing the TGF-β2 receptor in cancer cells triggers metastatic awakening. Aggressive breast cancer cells are either suppressed by alveolar macrophages or evade this suppression by avoiding interaction and downregulating the TGF-β2 receptor. Restoring TGF-βRIII in aggressive cells reinstates TGF-β2-mediated macrophage growth suppression. Thus, alveolar macrophages act as a metastasis immune barrier, and downregulation of TGF-β2 signaling allows cancer cells to overcome macrophage-mediated growth suppression.

DOI: 10.1016/j.cell.2024.09.016

Source: https://www.cell.com/cell/abstract/S0092-8674(24)01034-1