The long term objective of this proposal is to elucidate the interrelationships between the immune effector cells of Balb/c mice and their interactions with syngeneic mammary tumors of viral and non-viral origin developing in these hosts. The model systems to be employed include the Balb/cCrgl mouse colony where only endogenous mouse mammary tumor virus (MMTV) is present, Balb/cfC3H mice where in addition to the endogenous virus the exogenous MMTV has been introduced by foster nursing, and a colony of immunodeficient Balb/c mice which includes mice with inherited asplenia and heterozygous for the nude gene that have been shown to possess a very high incidence of spontaneous mammary tumors at an early age. The expression of MMTV-related antigens in lymphocytes will be analyzed at the transcriptional and translational levels in the Balb/cCrgl, Balb/cfC3H and in the immunodeficient Balb/c mice of the various genotypes. The relevance of endogenous MMTV as well as the modulating effects of exogenous virus to the host immune defenses will be assessed. Various regulatory cells detected in our previous studies that affect the responses to MMTV and to tumor associated antigens (TAA), will be analyzed by morphological, surface marker characteristics and functional activities. The mechanisms of action governing several cytotoxic reactions, i.e. NK, ADCC and innocent bystander cytotoxicity, will be scrutinized in the context of their effector cells, modulating factors and alterations during tumor growth. The possible reasons for the lack of responsiveness to TAA of the tumor infiltrating lymphocytes will be investigated. The proposed studies, which are logical derivations of our ongoing program, will help our understanding of the relative contributions of the various viral and tumor antigenic moieties and of the different types of lymphoreticular cells to the final outcome of the host-tumor interactions.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37CA025583-10
Application #
3482030
Study Section
Experimental Immunology Study Section (EI)
Project Start
1979-04-01
Project End
1991-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
10
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Miami School of Medicine
Department
Type
Schools of Medicine
DUNS #
City
Miami
State
FL
Country
United States
Zip Code
33101
Sun, Qi-Ling; Charyulu, Vijaya; Lobo, David et al. (2002) Role of thymic stromal cell dysfunction in the thymic involution of mammary tumor-bearing mice. Anticancer Res 22:91-6
Lopez, Diana M; Charyulu, Vijaya; Adkins, Becky (2002) Influence of breast cancer on thymic function in mice. J Mammary Gland Biol Neoplasia 7:191-9
Adkins, B; Charyulu, V; Sun, Q L et al. (2000) Early block in maturation is associated with thymic involution in mammary tumor-bearing mice. J Immunol 164:5635-40
Cheng, X; Lopez, D M (1998) CD4+, but not CD8+, T cells from mammary tumor-bearing mice have a down-regulated production of IFN-gamma: role of phosphatidyl serine. J Immunol 160:2735-41
Handel-Fernandez, M E; Lopez, D M (1998) Altered binding of the NF-GMa transcription factor is involved in the upregulated production of TNF-alpha by macrophages of mammary tumor bearing mice. Int J Mol Med 1:227-34
Handel-Fernandez, M E; Cheng, X; Herbert, L M et al. (1997) Down-regulation of IL-12, not a shift from a T helper-1 to a T helper-2 phenotype, is responsible for impaired IFN-gamma production in mammary tumor-bearing mice. J Immunol 158:280-6
DiNapoli, M R; Calderon, C L; Lopez, D M (1997) Phosphatidyl serine is involved in the reduced rate of transcription of the inducible nitric oxide synthase gene in macrophages from tumor-bearing mice. J Immunol 158:1810-7
Dinapoli, M R; Calderon, C L; Lopez, D M (1996) The altered tumoricidal capacity of macrophages isolated from tumor-bearing mice is related to reduce expression of the inducible nitric oxide synthase gene. J Exp Med 183:1323-9
Xie, Y; Fernandez, M E; Streilein, J W et al. (1996) Epidermal Langerhans cells from mice bearing a granulocyte macrophage-colony stimulating factor-producing mammary tumor display impaired accessory functions. Anticancer Res 16:9-16
Lopez, D M; Handel-Fernandez, M E; Cheng, X et al. (1996) Cytokine production by lymphoreticular cells from mammary tumor bearing mice: the role of tumor-derived factors. Anticancer Res 16:3923-9

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