Immunobiology of a spontaneously regressive tumor, the canine transmissible venereal sarcoma (review).

Canine transmissible venereal sarcoma (CTVS) is a contagious neoplasm of dogs that can be transplanted with intact viable cells across major histocompatibility (MHC) barriers among dogs and even other Canine such as foxes, coyotes, and jackals. After two to four months of progressive growth, the tumor regresses in adults, but metastasizes in immunosuppressed dogs and neonatally inoculated pups. The mechanisms of how the tumor cells manage to overcome histocompatibility barriers so successfully for such a long period and yet succumb later are not known. Immunologic studies have demonstrated serum antibodies in dogs that have the tumor. Tumor cells have been shown to contain a tumor-associated antigen (TAA). In contrast to TAA expression, cells from progressor tumors lacked the expression of either Class I or Class II MHC antigens whereas 30 to 40% of those from early regressor tumors expressed both Class I and Class II MHG antigens. This in turn may provoke additional immune reactions of the host to speed up the rejection process and cause the tumor mass to regress in two to three weeks. Tumors growing in adult dogs are smaller but infiltrated with greater numbers of lymphocytes than are the larger tumors growing in pups. Analyses of the neoplasms at different stages of growth have shown that regressing tumors contain higher numbers of lymphocytes, most of which are T cells. Electron microscopic studies have revealed that most cells in progressively growing tumors are round cells with microvilli, whereas those at steady-state and regressive stages are "transitional" cells with features that are intermediate between round cells and spindle-shaped fibroblastic cells. Regressing tumors have spindle-shaped cells with "abnormal" intracellular collagen bundles in vacuoles. Regressing tumors have spindle-shaped cells suggestive of tumor cell differentiation toward fibroblastic cells. It is tempting to speculate that lymphokines secreted by infiltrating lymphocytes may be important in the regression process by diffusion through the tumor mass to induce differentiation of round cells into spindle-shaped cells. CTVS is thus an experiment of nature showing that tumor cell differentiation and, in turn, spontaneous regression can be induced. Elucidation and exploitation of the underlying mechanism which is available in the body will be of great significance and practical importance.