Untitled

Abstract

Although macrophages (Ms) mediate tumor cytotoxicity, display tumor-associated antigens, and stimulate antitumor lymphocytes, cancer cells routinely circumvent these host-mediated immune activities, rendering the host incapable of mounting a successful antitumor immune response. Evidence supporting a direct causal relationship between cancer and immune dysfunction suggests that the presence of neoplastic tissue leads to immunologic degeneration. Furthermore, substantial data demonstrate that tumor growth adversely alters M function and phenotype. Thus, although Ms can serve as both positive and negative mediators of the immune system, the importance of Ms in tumor-induced immune suppression remains controversial. This review focuses on the evidence that tumor-derived molecules redirect M activities to promote tumor development. Tumors produce cytokines, growth factors, chemotactic molecules, and proteases that influence M functions. Many tumor-derived molecules, such as IL-4, IL-6, IL-10, MDF, TGF-␤ 1 , PGE 2 , and M-CSF, deactivate or suppress the cytotoxic activity of activated Ms. Evidence that tumor-derived molecules modulate M cytotoxicity and induce M suppressor activity is presented. This information further suggests that Ms in different in vivo compartments may be differentially regulated by tumor-derived molecules, which may deactivate tumor-proximal (in situ) M populations while concurrently activating tumordistal Ms, imparting a twofold insult to the host's antitumor immune response.