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.
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