Chernosky Noah M, Tamagno Ilaria
Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Case Comprehensive Cancer Center, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Cancers (Basel). 2021 Nov 10;13(22):5621. doi: 10.3390/cancers13225621.
Metastatic spread and recurrence are intimately linked to therapy failure, which remains an overarching clinical challenge for patients with cancer. Cancer cells often disseminate early in the disease process and can remain dormant for years or decades before re-emerging as metastatic disease, often after successful treatment. The interactions of dormant cancer cells and their metastatic niche, comprised of various stromal and immune cells, can determine the length of time that cancer cells remain dormant, as well as when they reactivate. New studies are defining how innate immune cells in the primary tumor may be corrupted to help facilitate many aspects of dissemination and re-emergence from a dormant state. Although the scientific literature has partially shed light on the drivers of immune escape in cancer, the specific mechanisms regulating metastasis and dormancy in the context of anti-tumor immunity are still mostly unknown. This review follows the journey of metastatic cells from dissemination to dormancy and the onset of metastatic outgrowth and recurrent tumor development, with emphasis on the role of the innate immune system. To this end, further research identifying how immune cells interact with cancer cells at each step of cancer progression will pave the way for new therapies that target the reactivation of dormant cancer cells into recurrent, metastatic cancers.
转移扩散和复发与治疗失败密切相关，而治疗失败仍是癌症患者面临的一项首要临床挑战。癌细胞通常在疾病进程的早期就发生播散，并且在成功治疗后，常常会在数年或数十年后重新出现转移病灶之前一直处于休眠状态。休眠癌细胞与其由各种基质细胞和免疫细胞组成的转移微环境之间的相互作用，能够决定癌细胞保持休眠的时间长短以及它们何时重新激活。新的研究正在明确原发性肿瘤中的固有免疫细胞是如何被破坏，从而有助于促进癌细胞从休眠状态播散和重新出现的诸多方面。尽管科学文献已部分揭示了癌症中免疫逃逸的驱动因素，但在抗肿瘤免疫背景下调节转移和休眠的具体机制仍大多未知。本综述追踪了转移细胞从播散到休眠以及转移灶生长和复发性肿瘤发展的过程，重点关注固有免疫系统的作用。为此，进一步研究确定免疫细胞在癌症进展的每个阶段如何与癌细胞相互作用，将为靶向休眠癌细胞重新激活为复发性转移性癌症的新疗法铺平道路。
