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.