The proposed research aims to use mouse mammary tumor models to investigate the relative involvement of T cells and macrophages when the host achieves immune control of tumor growth. The long-term objective of the research is to find ways to enhance the actions of effector cells that lead to restriction and control of tumor growth. Two different aspects of cellular immune resistance mechanisms will be studied: (1) The interactions of T cells and macrophages in the non-cytotoxic response seen in suboptimally immunized mice. This response produces encapsulation which leads to tumor dormancy and slow regression. The roles of T cells and macrophages in immuno-logically directed collagen deposition will be studied as an important factor in tumor encapsulation and dormancy. (2) The relative importance of T cells and macrophages in the acute cytotoxic tumor destruction seen in optimally immunized mice. Immuno-peroxidase staining with marker-specific monoclonal antibodies on frozen tumor sections will be used in morphometric analyses of the effector cell response in successful and unsuccessful resistance reactions at sequential stages of the developing immune response. The specific reactivity of T cell subsets and macrophages as accessory cells or effector cells will be studied by in vitro assay of tumor cell growth inhibition, using flow cytometry and also direct cell counting. The effects of immunopotentiation with interleukin-2, tumor necrosis factor, gamma interferon, and polyclonal and monoclonal anti-tumor antibodies will be studied.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA029660-07
Application #
3168829
Study Section
Experimental Immunology Study Section (EI)
Project Start
1980-07-01
Project End
1991-11-30
Budget Start
1987-12-01
Budget End
1988-11-30
Support Year
7
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Roswell Park Cancer Institute Corp
Department
Type
DUNS #
City
Buffalo
State
NY
Country
United States
Zip Code
14263
Vaage, J (1992) Immunologic aspects of fibrosis in mouse mammary carcinomas. Int J Cancer 50:69-74
Vaage, J (1992) Fibrosis in immune control of mammary-tumor growth. Int J Cancer 51:325-8
Vaage, J; Mayhew, E (1991) Immunotherapy of a mouse mammary carcinoma by sustained peritumor release of IL-2. Int J Cancer 47:582-5
Vaage, J (1991) Peri-tumor interleukin-2 causes systemic therapeutic effect via interferon-gamma induction. Int J Cancer 49:598-600
Vaage, J; Harlos, J P (1991) Collagen production by macrophages in tumour encapsulation and dormancy. Br J Cancer 63:758-62
Vaage, J; Donovan, D; Loftus, T (1991) Normal inhibition of mammary tumor metastasis in C3H/He mice. Clin Exp Metastasis 9:273-81
Vaage, J (1989) Loss of spontaneous metastasizing potential in mouse mammary tumors. Clin Exp Metastasis 7:373-8
Vaage, J (1988) Local interleukin 2 therapy of mouse mammary tumors of various immunogenicities. Cancer Res 48:2193-7
Vaage, J; Harlos, J P (1987) Spontaneous metastasis from primary C3H mouse mammary tumors. Cancer Res 47:547-50
Vaage, J; Pauly, J L; Harlos, J P (1987) Influence of the administration schedule on the therapeutic effect of interleukin-2. Int J Cancer 39:530-3

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