The development of breast cancer can be modulated by the actions of the immune system. Reciprocally, mammary tumors appear to cause profound alterations on the immunologically relevant cells, either directly, via tumor cell derived factors, or in an indirect manner. We propose to continue our studies to elucidate the interactions between the growing neoplasms and the immune effector cells using two well characterized mammary tumor systems. These tumors, which are syngeneic to BALB/c mice, allow the study of the effects of exogenous mammary tumor virus (MMTV) and its superantigen properties, and of other neoantigens appearing on mammary tumor cells of either viral etiology or chemically induced. We will specifically focus on the alterations observed in the lymphocytic compartment of these tumor bearing mice that have been detected in our ongoing studies. Specifically, we will (1) elucidate the molecular causes of the constitutive production of TNF-alpha by B cells from tumor bearing mice and the biological significance to the host of the overexpression of this pleiotropic cytokine; (2) we will investigate the role that MMTV plays in the downregulation of immune responses that occur during mammary tumor progression; (3) determine the mechanisms underlying the thymic involution observed in mammary tumor bearing mice; and (4) analyze the reasons for the altered cytokine expression in peripheral T cells from tumor bearing mice. An understanding of the causes for the immune deviations occurring during mammary tumorigenesis at the cellular and molecular levels, will help devise rational new therapeutic approaches for the eventual control of breast cancer.
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