Fidler IJ, Poste G.
Macrophage-mediated destruction of malignant tumor cells and new strategies for the therapy of metastatic disease.
Springer Seminars in Immunopathology. 1982;5(2):161–74.
[toggle_content title=”Abstract”] The propensity of malignant neoplasms to produce metastases in organs distant from the primary site is the principal cause of failure in the treatment of cancer. There are several reasons for the present lack of success in treating metastatic disease. First, at the time of diagnosis and excision of primary tumors, metastasis may have already occurred and the lesions are often too small to be detected. Moreover, widespread dissemination of metastases frequently takes place before symptoms of disease occur. Second, the anatomic location of many metastases may limit the effective dose of therapeutic agents that can be delivered to the lesions without being toxic to normal tissues or the host. The third, and most formidable problem, is that the phenotypic diversity of tumor cells in a single neoplasm is sufficiently great that the response of cells in metastatic lesions to therapy may differ from cells in the primary tumor, and individual metastases within the same patient may also respond differently to therapy [reviews, 12, 14, 41]. This problem means that successful treatment of metastatic disease will require the development of therapeutic regimens that can circumvent the cellular heterogeneity found in tumors and against which resistance is unlikely to develop. The role of macrophages in host defense against neoplasms has attracted increasing attention over the last few years [reviews, 4, 17, 39, 60]. This’stems in part from the disappointing results obtained in recent clinical efforts to augment host resistance to tumors by specific immunotherapy. In addition, there is a growing body of experimental evidence that macrophages are important effector cells in host defense against tumors and metastatic tumors in particular [review, 17]. Most important, activated tumoricidal macrophages are able to kill phenotypically diverse tumor cells, including cells that are resistant to killing by other components of the host defense system and various anticancer drugs [review, 17]. In this chapter we present a brief summary of current knowledge about the role of activated macrophages in host defense against metastasis and describe aspects of work done in our laboratories over the last few years using liposome-encapsulated macrophage activation agents to augment host resistance to metastatic tumors. [/toggle_content]