Yang T J
Department of Pathobiology, University of Connecticut, Storrs 06268.
Anticancer Res. 1988 Jan-Feb;8(1):93-5.
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.
犬传染性性病肉瘤（CTVS）是一种犬类传染性肿瘤，其完整的活细胞可跨越犬类之间的主要组织相容性（MHC）屏障进行移植，甚至能在狐狸、郊狼和豺等其他犬科动物之间移植。经过两到四个月的渐进性生长后，该肿瘤在成年犬中会消退，但在免疫抑制的犬和新生幼犬接种后会发生转移。肿瘤细胞如何如此成功地长期克服组织相容性屏障，却在后期消退，其机制尚不清楚。免疫学研究已在患有该肿瘤的犬体内检测到血清抗体。肿瘤细胞已被证明含有肿瘤相关抗原（TAA）。与TAA表达相反，进展期肿瘤的细胞缺乏I类或II类MHC抗原的表达，而早期消退期肿瘤的细胞中有30%至40%同时表达I类和II类MHC抗原。这反过来可能引发宿主的额外免疫反应，加速排斥过程，导致肿瘤块在两到三周内消退。成年犬体内生长的肿瘤较小，但与幼犬体内生长的较大肿瘤相比，浸润的淋巴细胞数量更多。对肿瘤不同生长阶段的分析表明，消退期肿瘤含有更多的淋巴细胞，其中大多数是T细胞。电子显微镜研究显示，渐进性生长肿瘤中的大多数细胞是具有微绒毛的圆形细胞，而处于稳定期和消退期的细胞是“过渡性”细胞，其特征介于圆形细胞和纺锤形成纤维细胞之间。消退期肿瘤具有纺锤形细胞，其空泡内有“异常”的细胞内胶原束。消退期肿瘤的纺锤形细胞表明肿瘤细胞正在向成纤维细胞分化。人们不禁推测，浸润淋巴细胞分泌的淋巴因子可能在消退过程中起重要作用，通过扩散穿过肿瘤块诱导圆形细胞分化为纺锤形细胞。因此，CTVS是一个自然实验，表明肿瘤细胞分化以及随之而来的自发消退是可以被诱导的。阐明和利用体内存在的潜在机制将具有重大的理论意义和实际重要性。
