Department of Infection, University College London (UCL), London, UK.
Immunol Rev. 2011 Mar;240(1):141-59. doi: 10.1111/j.1600-065X.2010.00987.x.
As man has moved rapidly from the hunter-gatherer environment to the living conditions of the industrialized countries, the incidences of some cancers have increased alarmingly. Recent increases are usually attributed to dietary changes or to altered exposures to putative carcinogens associated with the modern lifestyle. However, the changes in cancer incidence parallel similar increases in non-neoplastic chronic inflammatory disorders (inflammatory bowel disease, allergies, and autoimmunity), and the epidemiology is often strikingly similar. This parallel is worth exploring, because the increases in chronic inflammatory disorders are at least partly explained by immunoregulatory defects resulting from diminished exposure to microorganisms that co-evolved with mammals and developed a role in driving immunoregulatory circuits (the hygiene hypothesis). Dysregulated chronic inflammation can drive oncogenesis and also provides growth and angiogenic factors that enhance the subsequent proliferation and spread of tumor cells. Thus, a modern failure to downregulate inappropriate inflammation could underlie increases in some cancers in parallel with the increases in chronic inflammatory disorders. This possibility is supported by recent work showing that in some circumstances regulatory T cells protect against cancer, rather than aggravating it, as previously assumed. A greater understanding of these interactions might pave the way to improved microbe-based immunotherapies.
随着人类从狩猎采集环境迅速转变为工业化国家的生活条件，某些癌症的发病率惊人地上升。最近的发病率上升通常归因于饮食变化或与现代生活方式相关的潜在致癌物质暴露的改变。然而，癌症发病率的变化与非肿瘤性慢性炎症性疾病（炎症性肠病、过敏和自身免疫）的类似增加相平行，而且流行病学通常非常相似。这种平行值得探索，因为慢性炎症性疾病的增加至少部分可以通过免疫调节缺陷来解释，这些缺陷是由于与哺乳动物共同进化并在驱动免疫调节回路中发挥作用的微生物暴露减少所致（卫生假说）。失调的慢性炎症可驱动肿瘤发生，并提供生长和血管生成因子，从而增强随后肿瘤细胞的增殖和扩散。因此，现代未能下调不适当的炎症可能是某些癌症与慢性炎症性疾病同时增加的基础。最近的研究工作表明，在某些情况下，调节性 T 细胞可以预防癌症，而不是像以前认为的那样加重癌症，这支持了这种可能性。对这些相互作用的更深入了解可能为改进基于微生物的免疫疗法铺平道路。
