Anti-estrogens potentiate the immunotherapy of the P815 murine mastocytoma by cytotoxic T lymphocytes.
Many animal and human tumors are infiltrated with killer cells. Recent studies have shown that the stimulation of such killer cells with interleukin-2 improves their tumor rejecting capacity. In this paper we demonstrate that the anti-estrogens, tamoxifen (TX) and toremifene (TO), enhance host resistance by sensitizing the tumor target to killer cell mediated lysis. The P815 mastocytoma syngeneic to DBA/21 mice was used. Cytotoxic T lymphocytes (CTL) were detected in the spleens of mice 12-14 days after tumor inoculation. In vitro target, effector, or both cell types were treated with either TX (1 microM) or TO (5 microM) for 4 hours prior to cytotoxicity testing by 51Cr release. Mice bearing P815 mastocytomas, 5 mm in diameter, were treated orally with TX or TO and were given CTL isolated from the spleens of tumor bearing donors i.p. Tumor growth, mortality, and immunological memory in cured animals were monitored. Both TX and TO treatment sensitized P815 target cells to lysis by CTL isolated from tumor bearing animals. The transfer of killer cells from the spleens of tumor bearing mice produced tumor suppression in the recipients, which could be enhanced by additional oral treatment by TX or TO. Complete cure was achieved in a significant number of animals, showing partial or complete resistance to a subsequent lethal dose of P815 cells. These experiments indicate that killer cells isolated from mice bearing progressive tumors can have an immunotherapeutic effect in syngeneic tumor bearing recipients and that the antiestrogens, TX and TO, may be used to potentiate the immunotherapy of this tumor.
Nagy
E
E
Department of Immunology, Faculty of Medicine, University of Manitoba, Canada.
Baral
E
E
Kangas
L
L
Berczi
I
I
D019264:Adoptive Transfer; D000818:Animals; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D012515:Mast-Cell Sarcoma / Q000628:therapy*; D051379:Mice; D008811:Mice, Inbred DBA; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013629:Tamoxifen / Q000494:pharmacology*; D017312:Toremifene / Q000494:pharmacology*
D004965:Estrogen Antagonists; D013629:Tamoxifen; D017312:Toremifene