The research proposed here is an inquiry into the immunogenicity of and host response to human cutaneous melonoma. We will employ cultured cell lines from patients with primary and metastatic melanoma to probe for the following autologous cellular immune responses: the proliferative response of T cells, the generation of cell-mediated cytotoxicity to autochthonous tumor and the induction of suppression of autologous responsiveness. We will define the role of DR antigens in the immune response to autologous tumor and will employ anti-melanoma, monoclonal ("hybridoma") antibodies to define the non-DR antigens involved in such responses. From these studies we hope to understand something of the critical differences between biologically early primary disease and metastatic disease. Using a highly sensitive and quantitative assay for cell-associated immunoglobulin and complement, we will examine sera for antibody reactive to autologous melanoma. Monoclonal antibodes to melanoma will be used to search for specificities shared with naturally occurring antibodies. Immune complexes in patient sera will also be quantitated and their influence on in vitro cellular immunity will be assessed. Implicit in our research design is the longitudinal and correlative study of patients' serial cellular and humoral immune responses, of their sequentially cultured tumor and of their evolving clinical course. These studies should contribute to an understanding of the role of host immunity in the developmental biology of this human neoplasm. Such studies are of general importance to tumor immunology as melanoma (because of its easy detection and accessibility in the skin) can be investigated while the early and presumably most important host-tumor interactions take place. An understanding of these interactions should lead to clinically useful strategies to manipulate the immune response to melanoma and may well provide potentially useful diagnostic tools (e.g., serum factors indicative of micrometastatic disease).
NIH ExPorter
NIH ExPorter