The two aims of the present study are as follows: (1) The in vitro analysis of murine natural cell-mediated cytotoxicity (NCMC), especially NC and NK cells, which includes: (a) characterization of NCMC cells, especially NC, including definition of their surface phenotype and properties and production of long-term cell lines; (b) regulation of NCMC activity, especially genetic control and induction and/or augmentation of NCMC activity, especially by interleukins; (c) mechanisms of in vitro activity of NCMC; (d) characterization of susceptibleresistant tumor targets, especially cloned variants with differences in susceptibility to lysis, aiming at the definition of the target structures being recognized by NCMC effectors; and (e) correlation of the in vivo behavior of transplanted tumor target cells with their in vitro susceptibility to lysis, including their growth patterns in animals with NCMC deficiencies. (2) The in vivo analysis of tumor development and behavior in mice with spontaneous and/or induced deficiencies, especially NCMC: (a) using different chemical and viral carcinogens to determine tumor incidence and characteristics in animals with NC, NK, and/or other deficiencies; (b) studying the properties of the tumors arising in the above models, especially correlations with the NCMC deficiency of the host; and (c) completing the cycle by determining the effect of restoration of NCMC deficiency on tumor development. In essence, the study plans to continue the methodical and comprehensive reevaluation of the immunological surveillance concept, but as a non-thymus-dependent proposition, with the major stress on the NCMC system as the main candidate for being the mediator of such antitumor surveillance in mice. (SR)

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Immunobiology Study Section (IMB)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Sloan-Kettering Institute for Cancer Research
New York
United States
Zip Code
Glickstein, L; Macphail, S; Stutman, O (1996) Uncoupling IL-2 production from apoptosis and TNF production by changing the signal through the TCR. J Immunol 156:2062-7
Shih, S C; Stutman, O (1996) Cell cycle-dependent tumor necrosis factor apoptosis. Cancer Res 56:1591-8
Macphail, S; Stutman, O (1993) H-2 I-E molecules isolated from Mls1a stimulatory cells do not activate Mls1a-responsive T cells but do present exogenous staphylococcal enterotoxins. Eur J Immunol 23:90-5
Hernandez-Caselles, T; Stutman, O (1993) Immune functions of tumor necrosis factor. I. Tumor necrosis factor induces apoptosis of mouse thymocytes and can also stimulate or inhibit IL-6-induced proliferation depending on the concentration of mitogenic costimulation. J Immunol 151:3999-4012
Lattime, E C; Stutman, O (1992) WEHI-164 clone 2F: in vitro antitumor effects of tumor necrosis factor and gamma-interferon. Nat Immun 11:34-45
Lattime, E C; Stutman, O (1991) Antitumor immune surveillance by tumor necrosis factor producing cells. Immunol Res 10:104-13
Lattime, E C; Stutman, O (1989) Tumor growth in vivo selects for resistance to tumor necrosis factor. J Immunol 143:4317-23
Macphail, S; Stutman, O (1988) Anti-L3T4 antibody inhibits the lysis of H-2 class II antigen-negative target cells by L3T4+ cytotoxic T lymphocytes. Proc Natl Acad Sci U S A 85:5205-9
Lattime, E C; Stoppacciaro, A; Khan, A et al. (1988) Human natural cytotoxic activity mediated by tumor necrosis factor: regulation by interleukin-2. J Natl Cancer Inst 80:1035-8
Lattime, E C; Stoppacciaro, A; Stutman, O (1988) Limiting dilution analysis of TNF producing cells in C3H/HeJ mice. J Immunol 141:3422-8

Showing the most recent 10 out of 17 publications