El-Kenawi Asmaa, Hänggi Kay, Ruffell Brian
Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA.
Department of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA.
Cold Spring Harb Perspect Med. 2020 Apr 1;10(4):a037424. doi: 10.1101/cshperspect.a037424.
The dynamic interplay between neoplastic cells and the immune microenvironment regulates every step of the metastatic process. Immune cells contribute to invasion by secreting a cornucopia of inflammatory factors that promote epithelial-to-mesenchymal transition and remodeling of the stroma. Cancer cells then intravasate to the circulatory system assisted by macrophages and use several pathways to avoid recognition by cytotoxtic lymphocytes and phagocytes. Circulating tumor cells that manage to adhere to the vasculature and encounter premetastic niches are able to use the associated myeloid cells to extravasate into ectopic organs and establish a dormant microscopic colony. If successful at avoiding repetitive immune attack, dormant cells can subsequently grow into overt, clinically detectable metastatic lesions, which ultimately account to most cancer-related deaths. Understanding how disseminated tumor cells evade and corrupt the immune system during the final stages of metastasis will be pivotal in developing new therapeutic modalities that combat metastasis.
肿瘤细胞与免疫微环境之间的动态相互作用调控着转移过程的每一个步骤。免疫细胞通过分泌大量促进上皮-间质转化和基质重塑的炎性因子来促进侵袭。癌细胞随后在巨噬细胞的协助下进入循环系统，并利用多种途径避免被细胞毒性淋巴细胞和吞噬细胞识别。成功黏附于脉管系统并遇到前转移微环境的循环肿瘤细胞能够利用相关的髓样细胞外渗进入异位器官并建立一个休眠的微小菌落。如果成功避免反复的免疫攻击，休眠细胞随后可生长为明显的、临床可检测到的转移病灶，这最终导致了大多数与癌症相关的死亡。了解播散性肿瘤细胞在转移的最后阶段如何逃避和破坏免疫系统对于开发对抗转移的新治疗方法至关重要。
