Snyderman R, Pike M C
Am J Pathol. 1977 Sep;88(3):727-39.
There is considerable evidence to suggest that macrophages participate in host resistance to the development and spread of cancer. We have, therefore, studied monocytemacrophage function in humans and animals with neoplasms. Approximately 60% of patients with various types of cancer were found to have abnormal monocyte chemotactic responsiveness in vitro, and abnormal chemotaxis was an indicator of poor prognosis in patients with melanoma. By studying patients before and after surgery, it was found that abnormal chemotactic responses normalized within weeks after removal of malignant tumors, indicating that a neoplasm itself might affect the host's monocyte chemotactic responsiveness. Subsequent studies using transplantable neoplasms in mice substantiated this hypothesis in that macrophage accumulation in vivo as well as macrophage chemotactic responsiveness in vitro was depressed in animals during the early phases of tumor growth. This depression of macrophage function could be attributed to a low-molecular-weight factor contained in murine neoplasms, which when given to normal mice was extremely potent in depressing peritoneal macrophage accumulation and chemotaxis but, paradoxically, enhanced phagocytosis. The serum of tumor-bearing mice also contained potent inhibitory activity for macrophage accumulation. In contrast to the effects on macrophages, granulocyte accumulation in vivo and chemotaxis in vitro was not depressed by the presence of a neoplasm or the administration of the factor from neoplasms. By releasing factors which depress macrophage migratory function, neoplasms may protect themselves from immunologically mediated host destruction during the early phases of tumor growth.
有大量证据表明巨噬细胞参与宿主对癌症发生和扩散的抵抗。因此，我们研究了患有肿瘤的人类和动物的单核细胞 - 巨噬细胞功能。发现约60%的各类癌症患者在体外单核细胞趋化反应异常，而趋化异常是黑色素瘤患者预后不良的指标。通过对手术前后患者的研究发现，去除恶性肿瘤后数周内，异常的趋化反应恢复正常，这表明肿瘤本身可能影响宿主的单核细胞趋化反应性。随后使用小鼠可移植肿瘤的研究证实了这一假设，即在肿瘤生长早期，动物体内的巨噬细胞积聚以及体外巨噬细胞趋化反应性均受到抑制。巨噬细胞功能的这种抑制可归因于小鼠肿瘤中含有的一种低分子量因子，将其给予正常小鼠时，它在抑制腹腔巨噬细胞积聚和趋化方面极具效力，但矛盾的是，它增强了吞噬作用。荷瘤小鼠的血清对巨噬细胞积聚也有强大的抑制活性。与对巨噬细胞的影响相反，肿瘤的存在或肿瘤因子的施用并未抑制体内粒细胞积聚和体外趋化作用。通过释放抑制巨噬细胞迁移功能的因子，肿瘤在生长早期可能保护自身免受免疫介导的宿主破坏。
