Summary
Eight spontaneously occurring solid canine tumors were transplanted subcutaneously into six normal adult dogs immunosuppressed by Cyclosporin A (CyA). Five of six osteogenic sarcomas (OS) and the single thyroid adenocarcinoma proliferated into macroscopic tumors; one OS and the single mastocytoma failed to grow. When CyA treatment was stopped, all but one of the tumors were rejected. Biopsies obtained during CyA administration showed minimal necrosis and inflammation in the tumor. After CyA was stopped, dense lymphocytic infiltrates and marked tumor necrosis were observed. Tissue slices of two lymphomas, single-cell suspension of four lymphomas, and three OS and cells from the OS-derived cell lines D22 and 113 given subcutaneously and intradermally failed to proliferate. Reactivity of lymphocytes from transplante recipients in mixed leukocyte cultures was normal when carried out in normal serum but was suppressed profoundly when serum from the CyA-treated dog was added. These data suggest that CyA allows for engraftment of allogeneic tumors in normal dogs by interfering with host T-lymphocyte function. This model may allow the study of the efficacy of various antitumor treatment regimens in a large animal.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bertschmann M, Scharen B, Luscher EF (1979) Correlation of in vivo and in vitro immune reactions against the intradermally developing P-815 mastocytoma in the syngeneic mouse. Immunobiology 156:382
Betton GR, Owen LN (1976) Allogeneic grafts of spontaneous canine melanomas and their cell culture strains in neonatal immunosuppressed dogs. Br J Cancer 34:374
Bowles CA, Kerber WT, Rangan SRS, Kwapien R, Woods W, Jensen EM (1972) Characterization of a transplantable, canine, immature mast cell tumor. Cancer Res 32:1434
Calne RY (1979) Immunosuppression for organ grafting — observations on cyclosporin A. Immunol Rev 46:113
Campanile F, Crino L, Bonmassar E, Houchens D, Goldin A (1977) Radioresistant inhibition of lymphoma growth in congenitally athymic (nude) mice. Cancer Res 37:394
Cohen H, Chapman AL, Ebert JW, Bopp WJ, Gravelle CR (1970) Cellular transmission of canine lymphoma and leukemia in beagles. J Natl Cancer Inst 45:1013
Deeg HJ, Storb R, Gerhard-Miller L, Shulman HM, Weiden PL, Thomas ED (1980) Cyclosporin A, a powerful immunosuppressant in vivo and in vitro in the dog, fails to induce tolerance. Transplantation 29:230
Deeg HJ, Storb R, Atkinson K, Weiden PL, Severns E, Thomas ED (1981) Long-term survival of dogs given unrelated DLA nonidentical marrow grafts and cyclosporin A (CyA) and methotrexate (MTX) — tolerance mediated by nylon-wool adherent suppressor cells? Exp Hematol [Suppl 9] 9:94
Eccles SA, Heckford SE, Alexander P (1980) Effect of cyclosporin A on the growth and spontaneous metastasis of syngeneic animal tumors. Br J Cancer 42:252
Fefer A, Cheever MA, Greenberg PD (to be published) Lymphocyte transfer as potential cancer immunotherapy. In: Immunological aspects of cancer therapeutics. Wiley, New York
Gordon MY, Singer JW (1979) The effects of cyclosporin A on colony-formation by human lymphoid and myeloid cells. Nature 279:433
Gratwohl A, Forster I, Speck B (1981) Skin grafts in rabbits with cyclosporin A: absence of induction of tolerance and untoward side effects. Transplantation 31:136
Homan WP, Williams KA, Fabre JW, Millard PR, Morris PJ (1981) Prolongation of cardiac xenograft survival in rats receiving cyclosporin A. Transplantation 31:164
Introna M, Allavena P, Spreafico F, Mantovani A (1981) Inhibition of human natural killer activity by cyclosporin A. Transplantation 31:113
Kakuk TJ, Hinz RW, Langham RF, Conner GH (1968) Experimental transmission of canine malignant lymphoma to the beagle neonate. Cancer Res 28:716
Lems SPM, Koene RAP (1979) Prolongation of mouse skin allograft survival by cyclosporin A: graft rejection after withdrawal of therapy. IRCS Med Sci 7:184
Moldovanu G (1970) Serial cellular transmission of canine lymphoma. Bibl Haematol 36:416
Ochs HD, Storb R, Thomas ED, Kolb H-J, Graham TC, Mickelson E, Parr M, Rudolph RH (1974) Immunologic reactivity in canine marrow graft recipients. J Immunol 113:1039
Owen LN (1973) Transplantation of canine lymphocytic leukaemia. In: Bibl Haematol 39:139
Owen LN, Morgan DR, Bostock DE, Flemans RJ (1977) Tissue culture and transplantation studies on canine mammary carcinoma. Eur J Cancer 13:1445
Paavonen T, Hayry P (1980) Effect of cyclosporin A on T-dependent and T-independent immunoglobulin synthesis in vitro. Nature 287:542
Penn I (1978) Malignancies associated with immunosuppressive or cytotoxic therapy. Surgery 83:492
Shifrine M, Wilson FD (eds) (1980) The canine as a biomedical research model: Immunological, hematological and oncological aspects. National Technical Information Service, U.S. Department of Energy, Springfield, Virginia (DOE/TIC-10191)
Talmadge JE, Meyers KM, Prieur DJ, Starkey JR (1980) Role of NK cells in tumour growth and metastasis in beige mice. Nature 284:622
Tutschka PJ, Beschorner WE, Allison AC, Burns WH, Santos GW (1979) Use of cyclosporin A in allogeneic bone marrow transplantation in the rat. Nature 280:148
Weiden PL, Storb R, Tsoi M-S, Deeg HJ, Graham TC (1978) Canine osteosarcoma: results of amputation with and without adjuvant immunotherapy. Cancer Immunol Immunother 5:181
Zalewski AA, Gulati AK (1981) Rejection of nerve allografts after cessation of immunosuppression with cyclosporin A. (Brief communication) Transplantation 31:88
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Deeg, H.J., Hackman, R.C., Weiden, P.L. et al. Growth of canine tumors transplanted into normal adult dogs immunosuppressed by Cyclosporin A. Cancer Immunol Immunother 12, 147–152 (1982). https://doi.org/10.1007/BF00205373
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00205373