Deparment of Surgery, L.D. MacLean Surgical Research Laboratories, McGill University Health Centre, McGill University, Montreal, Canada.
Montreal General Hospital, Room L8-505, 1650 Cedar Avenue, Montreal, QC, H3G 1A4, Canada.
Clin Exp Metastasis. 2020 Apr;37(2):225-239. doi: 10.1007/s10585-020-10018-2. Epub 2020 Jan 23.
Cancer is the leading cause of death in North America. Despite modern advances in cancer therapy, many patients will ultimately develop cancer metastasis resulting in mortality. Surgery to resect early stage solid malignancies remains the cornerstone of cancer treatment. However, surgery places patients at risk of developing post-operative infectious complications that are linked to earlier cancer metastatic recurrence and cancer mortality. Toll-like receptors (TLRs) are evolutionarily-conserved sentinel receptors of the innate immune system that are activated by microbial products present during infection, leading to activation of innate immunity. Numerous types of solid cancer cells also express TLRs, with their activation augmenting their ability to metastasize. Similarly, healthy host-tissue TLRs activated during infection induce a prometastatic environment in the host. Cancer cells additionally secrete TLR activating ligands that activate both cancer TLRs and host TLRs to promote metastasis. Consequently, TLRs are an attractive therapeutic candidate to target infection-induced cancer metastasis and progression.
癌症是北美地区的主要死亡原因。尽管癌症治疗在现代取得了进步，但许多患者最终会发展为癌症转移，导致死亡。切除早期实体恶性肿瘤的手术仍然是癌症治疗的基石。然而，手术使患者面临发生术后感染性并发症的风险，这些并发症与癌症转移复发和癌症死亡率的早期升高有关。Toll 样受体（TLR）是固有免疫系统中进化保守的哨兵受体，可被感染时存在的微生物产物激活，从而导致固有免疫的激活。许多类型的实体癌细胞也表达 TLR，其激活增强了它们转移的能力。同样，感染期间健康宿主组织 TLR 的激活会在宿主中诱导出有利于转移的环境。癌细胞还分泌 TLR 激活配体，激活癌症 TLR 和宿主 TLR，以促进转移。因此，TLR 是一种有吸引力的治疗候选物，可用于靶向感染诱导的癌症转移和进展。
