Antiinflammatory proteins associated with human and murine neoplasms

Abstract

The immune mechanisms by which a host recognizes and destroys a growing tumor are undoubtedly complex and, as yet, incompletely understood. It is apparent, however, that mononuclear phagocytes play an important role in the defense against neoplastic disease and that the ability of monocytes and macrophages to accumulate at and within a growing tumor is a strict requirement for them to effect that role. Studies from our laboratory as well as those of other investigators have demonstrated that patients with a variety of neoplastic diseases have a specific defect in monocyte chemotactic responsiveness and that this defect is associated with the presence of the tumor. Furthermore, we and others have shown that a similar defect occurs in tumor-bearing rodents, thus allowing model systems to be developed for the study of the mechanisms involved. We have demonstrated that transplanted, spontaneous or carcinogen-induced murine tumors produce low molecular weight proteins which inhibit the accumulation of macrophages to inflammatory foci and that a significant portion, if not all, of these proteins are physicochemically and antigenically related to the retroviral envelope protein p15E. We have shown that p15E itself can inhibit the inflammatory accumulation of macrophages in normal mice. Studies on a wide variety of cancer patients have revealed that the fluids of such patients contain proteins which inhibit the responses of normal monocytes to various chemotaxins and, as in tumor-bearing mice, that these antiinflammatory proteins are antigenically related to retroviral p15E. Recent studies have demonstrated that human tumor cells can simultaneously release factors which are chemotactic for monocytes with those which are p15E-related inhibitors of chemotactic responsiveness, suggesting that the mononuclear phagocyte response to a growing tumor may be, in part, dictated by the balance obtained between various proteins produced by that tumor. The isolation and characterization of endogenous retroviral sequences within the human genome and the observation that the envelope genes of these endogenous sequences are partially homologous to p15E provide potential candidates for the p15E-related inhibitors of chemotactic responses which have been identified from human cancer cells and fluids. Studies now under way in a number of laboratories should provide more definitive answers regarding the nature and source of these p15E-related inhibitors.(ABSTRACT TRUNCATED AT 400 WORDS)