Salama Paul, Platell Cameron
School of Surgery and Pathology, University of Western Australia, Perth, Western Australia, Australia.
ANZ J Surg. 2008 Sep;78(9):745-53. doi: 10.1111/j.1445-2197.2008.04642.x.
It has long been established that inflammation and immunity play critical roles in the pathogenesis, control and eventual metastasis of cancers. With the advent of more sophisticated animal models and immunohistochemical techniques a greater understanding of the immune system and its interactions has occurred. Individual immune cells are dynamic structures that have variable behaviour controlled by complex interactions in the tumour microenvironment. In the setting of colorectal cancer it was first observed that peritumoral inflammatory infiltrates were associated with improved prognosis. Immunohistochemistry has shown the individual cells types within these infiltrates. It now appears that an adaptive immune response, differentiated along the T-helper 1 pathway controls tumour invasion and metastasis. Furthermore, the immune system exerts selection pressure leading to the evolution of tumour cell variants that can induce tolerance and disable adaptive immunity. These tumour cells then use the mechanisms of innate immunity to facilitate further growth, angiogenesis, invasion and eventual metastasis. These issues are investigated with particular relevance to colorectal cancer. Using the immune response to defeat CRC has been under intense investigation but has so far been unsuccessful. Nevertheless, researchers remain optimistic that immunotherapy will play an important role in the treatment of this common disease.
长期以来,炎症和免疫在癌症的发病机制、控制及最终转移过程中发挥着关键作用。随着更复杂的动物模型和免疫组织化学技术的出现,人们对免疫系统及其相互作用有了更深入的了解。单个免疫细胞是动态结构,其行为受肿瘤微环境中复杂相互作用的控制而变化。在结直肠癌的情况下,人们首先观察到肿瘤周围的炎性浸润与预后改善相关。免疫组织化学已显示出这些浸润中的单个细胞类型。现在看来,沿辅助性T细胞1途径分化的适应性免疫反应控制着肿瘤的侵袭和转移。此外,免疫系统施加选择压力,导致肿瘤细胞变体的进化,这些变体可诱导耐受并使适应性免疫失效。然后这些肿瘤细胞利用固有免疫机制促进进一步生长、血管生成、侵袭及最终转移。本文特别针对结直肠癌对这些问题进行了研究。利用免疫反应战胜结直肠癌一直是深入研究的课题,但迄今为止尚未成功。尽管如此,研究人员仍乐观地认为免疫疗法将在这种常见疾病的治疗中发挥重要作用。