Department of Dermatology, Harvard Institutes of Medicine, Boston, MA 02115, USA.
Adv Exp Med Biol. 2013;734:145-79. doi: 10.1007/978-1-4614-1445-2_8.
Increasing evidence suggests that tumor dormancy represents an important mechanism underlying the observed failure of existing therapeutic modalities to fully eradicate cancers. In addition to its more established role in maintaining minimal residual disease after treatment, dormancy might also critically contribute to early stages of tumor development and the formation of clinically undetectable micrometastatic foci. There are striking parallels between the concept of tumor dormancy and the cancer stem cell (CSC) theory of tumor propagation. For instance, the CSC hypothesis similarly predicts that a subset of self-renewing cancer cells-that is CSCs-is responsible for tumor initiation, bears the preferential ability to survive tumor therapy, and persists long term to ultimately cause delayed cancer recurrence and metastatic progression. Additionally, many of the biological mechanisms involved in controlling the dormant state of a tumor can also govern CSC behavior, including cell cycle modifications, alteration of angiogenic processes, and modulation of antitumor immune responses. In fact, quiescence and immune escape are emerging hallmark features of at least some CSCs, indicating significant overlap between dormant cancer populations and CSCs. Herein, we crucially dissect whether CSCs occupy specific roles in orchestrating the switch between dormancy and exuberant tumor growth. We elucidate how recently uncovered CSC biological features could enable these cells to evade immunologic clearance and regulate cancer expansion, relapse, and progression. We propose that the study of CSC immunobiological pathways holds the promise to critically advance our understanding of the processes mediating tumor dormancy. Ultimately, such research endeavors could unravel novel therapeutic avenues that efficiently target both proliferating and dormant CSCs to minimize the risk of tumor recurrence in cancer patients.
越来越多的证据表明，肿瘤休眠是现有治疗方法未能完全根除癌症的重要机制之一。休眠除了在治疗后维持微量残留疾病方面的作用更为明确外，还可能对肿瘤发展的早期阶段和临床不可检测的微转移灶的形成起关键作用。肿瘤休眠的概念与肿瘤传播的癌症干细胞（CSC）理论之间存在惊人的相似之处。例如，CSC 假说同样预测，一小部分自我更新的癌细胞——即 CSCs——负责肿瘤的起始，具有优先的存活肿瘤治疗的能力，并长期存在，最终导致癌症复发和转移进展的延迟。此外，控制肿瘤休眠状态的许多生物学机制也可以控制 CSC 的行为，包括细胞周期修饰、血管生成过程的改变和抗肿瘤免疫反应的调节。事实上，静止和免疫逃逸是至少一些 CSCs 的新兴标志特征，这表明休眠的癌症群体和 CSCs 之间存在显著的重叠。在此，我们将深入探讨 CSCs 是否在调控休眠和肿瘤过度生长之间的转换中发挥特定作用。我们阐明了最近发现的 CSC 生物学特征如何使这些细胞能够逃避免疫清除并调节癌症的扩张、复发和进展。我们提出，研究 CSC 的免疫生物学途径有望极大地提高我们对介导肿瘤休眠的过程的理解。最终，这些研究工作可以揭示出有效的靶向增殖和休眠 CSCs 的新治疗途径，以最大限度地降低癌症患者肿瘤复发的风险。
