Macrophage migratory dysfunction in cancer. A mechanism for subversion of surveillance.
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.
D000818:Animals; D001943:Breast Neoplasms / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000276:immunology; D002464:Cell Migration Inhibition; D002634:Chemotaxis, Leukocyte; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology; D008223:Lymphoma / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008545:Melanoma / Q000276:immunology; D051379:Mice; D009000:Monocytes / Q000276:immunology; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000276:immunology*; D010587:Phagocytosis; D012513:Sarcoma, Experimental / Q000276:immunology; D012878:Skin Neoplasms / Q000276:immunology; D013724:Teratoma / Q000276:immunology