Ribosomopathies are defined as inherited diseases in which ribosomal factors are mutated. In general, they present multiorgan symptoms. In spite of the fact that in cellular models, ribosomal insufficiency leads to a reduced rate of oncogenic transformation, patients affected by ribosomopathies present a paradoxical increase in cancer incidence. Several hypotheses that explain this paradox have been formulated, mostly on the assumption that altered ribosomes in a stem cell induce compensatory changes that lead to a cancer cell. For instance, the lack of a specific ribosomal protein can lead to the generation of an abnormal ribosome, an oncoribosome, that itself leads to altered translation and increased tumorigenesis. Alternatively, the presence of ribosomal stress may induce compensatory proliferation that in turns selects the loss of tumor suppressors such as p53. However, modern views on cancer have shifted the focus from the cancer cell to the tumor microenvironment. In particular, it is evident that human lymphocytes are able to eliminate mutant cells and contribute to the maintenance of cancer-free tissues. Indeed, many tumors develop in conditions of reduced immune surveillance. In this review, we summarize the current evidence and attempt to explain cancer and ribosomopathies from the perspective of the microenvironment.
核糖体病被定义为核糖体因子发生突变的遗传性疾病。这类疾病通常表现为多器官症状。尽管在细胞模型中，核糖体功能不足会降低致癌转化率，但核糖体病患者却呈现出癌症发病率异常升高的矛盾现象。针对这一悖论，已有多种假说被提出，大多基于以下假设：干细胞中异常的核糖体会引发代偿性变化，最终导致癌细胞的形成。例如，特定核糖体蛋白的缺失可能导致异常核糖体——即癌性核糖体的产生，这种核糖体本身会引起翻译过程改变并增强肿瘤发生。另一种可能是，核糖体应激的存在可能诱发代偿性增殖，进而选择性地导致p53等肿瘤抑制因子的缺失。然而，现代癌症研究已将焦点从癌细胞转向肿瘤微环境。特别是，人类淋巴细胞能够清除突变细胞并维持组织无癌状态的观点已得到证实。事实上，许多肿瘤是在免疫监视减弱的情况下发展的。本综述总结了现有证据，并尝试从微环境角度解释癌症与核糖体病之间的关联。
肿瘤(癌症)患者之家