Our recent research efforts have been focused upon studying the immunoregulatory biology of peritoneal cavity leucocytes. Interest in assessing the antigen presenting capability of B cell subsets led to comparison of spleen (enriched for B-2 or conventional B cells) and peritoneal cavity (enriched for the B-1 subset) B cells. Serendipitously, this work led to the discovery of potent immune suppression mediated by peritoneal macrophages (M?s). We found that M? suppression of T cell activation is mediated by amino acid catabolism. This suppression is cell concentration-dependent as lower numbers of the same M?s functioned as effective antigen presenting cells (APCs). Growing evidence of immune dysregulation in M?-rich tumors fostered our interest in studying the biology of M?- lymphocyte interaction. This proposal outlines experiments in which we characterize an in vitro model of the altered immune composition of the tumor microenvironment. The model will serve as an initial screen for therapies designed to reverse the immune suppression evidenced in many tumors.
Although the components necessary for a proper immune response to cancer are often found within the tumor these cells are rendered ineffective by the tumor microenvironment. Understanding the cellular and molecular basis for this immune-regulation will afford novel strategies for therapeutic intervention. Cancer treatment via nontoxic immunobiologic modulation will avoid the toxicity associated with current chemo- and radio-therapeutic practices.
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