There is increasing evidence that natural killer (NK) cells may play an important role in resistance against growth of tumors in vivo. However, most of the studies on NK cell-mediated cytotoxicity have focused on in vitro studies, and only a limited number of investigations concerning NK cells in vivo antitumor potential have been done.
The aim of our studies was to investigate involvement of NK cells in in vivo resistance to murine tumors. Using murine ascitic mammary adenocarcinoma 755 model, we found a correlation between augmentation of NK cell cytotoxicity and resistance to the growth of 755 tumor. Specifically, NK cell inducer of pyrimidinone group, 2-amino-5-iodo-6-phenyl-4 pyrimidinol (AIPP), induced high levels of NK cell activity in peritoneal cavity concomitantly with high resistance of B6D2F?1? mice to the growth of 755 tumor, the tumor that grew rapidly in control mice. Additionally, such tumor-protective effect was abrogated when the AIPP-stimulated mice were treated with NK cell-specific antiserum NK.1 but not with T-cell-directed antiserum Thy 1.2. These experiments suggest that NK cells are involved in resistance to mammary adenocarcinoma 755 and suggest that AIPP may be a useful therapeutic agent. The studies on the mechanism of NK cell augmentation indicate that both NK cell tumor-binding, as well as tumor lytic capacity, was augmented by AIPP and that such augmentation was mediated by regionally induced interferon. (HF)

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National Cancer Institute (NCI)
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Experimental Therapeutics Subcommittee 2 (ET)
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University of Texas MD Anderson Cancer Center
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Savary, C A; Lotzova, E (1987) Mechanism of decline of natural killer cell activity in Corynebacterium parvum-treated mice: inhibition by erythroblasts and Thy 1.2+ lymphocytes. J Natl Cancer Inst 79:533-41
Drewinko, B; Moskwa, P; Lotzova, E et al. (1986) Successful heterotransplantation of human colon cancer cells to athymic animals is related to tumor cell differentiation and growth kinetics and to host natural killer cell activity. Invasion Metastasis 6:69-82
Lotzova, E; Savary, C A; Lowlachi, M et al. (1986) Cytotoxic and morphologic profile of endogenous and pyrimidinone-activated murine NK cells. J Immunol 136:732-40
Lotzova, E; Savary, C A (1986) Pyrimidinones: inducers of NK cell activity and antitumor immunity. Comp Immunol Microbiol Infect Dis 9:185-91
Lotzova, E; Savary, C A; Pollack, S et al. (1986) Induction of tumor immunity and natural killer cell cytotoxicity in mice by 5-halo-6-phenyl pyrimidinone. Cancer Res 46:5004-8
Lotzova, E (1986) Therapeutic possibilities of virus-modified tumor cell extracts and interleukin-2 in human ovarian cancer. Nat Immun Cell Growth Regul 5:277-82
Lotzova, E; Savary, C A; Freedman, R et al. (1986) Natural immunity against ovarian tumors. Comp Immunol Microbiol Infect Dis 9:269-75
Lotzova, E (1985) Effector immune mechanisms in cancer. Nat Immun Cell Growth Regul 4:293-304
Rao, P N; Wang, Y C; Lotzova, E et al. (1985) Antitumor effects of gossypol on murine tumors. Cancer Chemother Pharmacol 15:20-5
Savary, C A; Lotzova, E; Gray, K N et al. (1985) Natural killer cell-mediated antitumor reactivity of rhesus monkeys. Nat Immun Cell Growth Regul 4:328-39