The pathogenesis of metastasis is a complex biological process with many interacting factors. The role of immune response in the control of metastasis, though recognized as one of the important factors, is still poorly understood. Concomitant tumor immunity (CTI) to both autochthonous and syngenic tumors is strikingly potent in terms of the size of tumor cell challenge it is capable of rejecting [51,71]. The observation that tumors that are highly metastatic have poor CTI [23,46] indicates that immune response to a progressive tumor has a potent role in controlling the metastatic spread.Increased metastasis observed following generalized immunosuppression [7, 20,41,60] or specific suppression of T cells [11, 15] and macrophages [8,34] and in deficiency of natural killer cell activity such as is normal in beige mice [68] indicates the role of different components of the immune system in the control of metastasis.However, studies on the cells infiltrating the tumor, which would reflect the immune control at the site of the tumor, have given varied results. The nature of infiltrating cells within the tumor mass varies from tumor to tumor, and the nature of effector cells found within the tumor may or may not correlate with what is found in the spleen or peripheral lymph nodes or in the blood of the same tumor-bearing animals [28]. Husby et al. [33] have shown that T cells predominante in the infiltrates of primary tumors and the pattern remains the same regardless of anatomic site or of the presence or absence of metastasis. In contrast, B cells predominate at the margin of a metastasis. Mononuclear cells bearing Fc receptors were not a prominent component of the infiltrate associated with either primary tumor or metastasis. Currie [10] and Alexander and Eccles [2] have shown that metastatic tumors contain Reprint request should be addressed to: M. Seshadri few macrophages and the localized tumors contain a wide range, but tending toward a higher number of macrophages. Nonmetastasizing and metastasizing lymphomas produce similar responses in the lymph node weight gain assay, but host cell infiltration in the tumor growing subcutaneously was much greater in nonmetastasizing than in metastasizing tumors. The infiltrating cells were found to be Fc receptor-positive, and matured into macrophages after 2 days in culture [11]. In experimental systems, macrophage infiltration has been found to be directly proportional to immunogenicity and inversely proportional to metastatic capacity [13]. Dependence of macrophage infiltration on the thymic function has been shown in studies where heterozygous nude mice show higher infiltration into tumors than do homozygous nude mice [64], and animals subjected to thymectomy and irradiation show less infiltration into tumors than normal mice [13]. Thus macrophage infiltration might reflect host immune reaction to the tumor. In keeping with a contribution of the infiltrating cells to the control of metastasis, when tumor cells were depleted of macrophages before implantation an increas...
