肿瘤休眠细胞:复发根源和治疗靶标

Dormant tumor cells:Root for recurrence and target for therapy

随着肿瘤早期诊断及治疗水平的提高,肿瘤患者的无病生存率得以提高,但仍面临着较高的肿瘤复发风险。越来越多的证据显示,这些长期无病生存的肿瘤患者(甚至某些所谓健康人)的机体内存在着一种肿瘤休眠细胞,这些细胞被认为是导致肿瘤复发的主要根源。肿瘤休眠细胞是一群存在于患者或健康人群体内的数量极少且难以检测的静止细胞,目前对其形成的机制及休眠活动的时相规律均不十分清楚。对于患者而言,骨髓和外周血取材比较容易,所以人们通常会针对骨髓及外周血中的肿瘤休眠细胞建立相对敏感的检测方法。有证据显示,免疫抑制、新生血管生成及外科手术等因素可使肿瘤休眠细胞激活,从而引发肿瘤的复发和转移。肿瘤休眠细胞已成为我们根治肿瘤及预防肿瘤发生或复发的重要靶标。然而,由于处于休眠期的肿瘤细胞不发生活跃增殖,因此传统放、化疗不能将其有效清除,从而对肿瘤的彻底治愈造成了极大的困难。研究表明,免疫监控与肿瘤休眠现象高度相关,因此,针对肿瘤休眠细胞的肿瘤免疫过继细胞治疗将给肿瘤防治带来根本性的变革。我们相信,随着对肿瘤休眠细胞研究的不断深入,将会出现高效清除肿瘤休眠细胞或使肿瘤细胞永远休眠的崭新治疗方案。

With the fast development of early diagnosis and treatment for cancers, the survival rates of victims of this deadly disease has been greatly increased. Yet the survivors still face the threat of reoccurrence. More and more evidence documented that these disease-free patients （and even some so-called healthy people） harbor dormant tumor cells, which are now regarded as the main cause for tumor reoccurrence. Dormant tumor cells refer to a group of cells featured by its minimal number and the inconvenience for detection. These cells are caught in cell cycle arrest and can exist in both pa- tients and healthy people. At present, the mechanism of how these cells are formed and dormancy timing patterns are still unknown. As the bone marrow and peripheral blood of patients are easy obtained, sensitive detection method has been es- tablished aimed to detect dormant tumor cells from these two sources. Evidence has shown that immunological suppression, angiogenesis in tumor tissues as well as surgery may all play roles in tumor dormancy activation, and thus lead to tumor re- occurrence and metastasis. As a result, dormant tumor cells have become a crucial target for preventing and treating canc- ers. However, since dormant tumor cells stay in a tranquil state, they are insensitive to traditional clinical therapies inclu- ding radiation treatment and chemotherapy, and therefore impose great difficulty for the radical cure. According to the lat- est research, immune surveillance is closely related to the phenomena of tumor dormancy. As a result, adoptive immuno- therapy may bring radical revolution in the area of tumor prevention and treatment. We hope that, with the deepening of research on tumor dormancy, clinical options with high efficiency will be available to wipe out tumor cells or induce tumor cells into permanent dormancy.