Cloning Of Mouse B7-H4 CDNA, Construction Of Its Recombinant Adenovirus And Investigation Of Its Role In Tumor's Immune Escape

The majority of human and rodent cancers display various antigens, which could elicit cellular and humoral immune responses. Such immunity, however, often fails to prevent progressive growth of cancers. It has long been speculated that tumor antigens may not be presented in appropriate fashion, which subsequently fails to elicit a strong immune response. According to these hypothesis, cancer vaccines, which are based on tumor antigen formulated with various immune stimulatory content such as adjuvant, viral vector, dendritic cells et al. could often enhance T cell responses against cancer antigens in experimental animals and in advanced cancer patients. However, cancers in the majority of these patients progress continuously. Furthermore, adoptive transfer of large number of pre-activated T cells to bypass the priming process in vivo has limited impact in the regression of cancers. Therefore, existence of active immune responses to cancer antigens in patients does not always correlate with elimination of cancer cells in vivo. These clinical observations thus are consistent with the findings that cancer cells often develop evasion mechanisms in their microenvironment, which protect cancer cells from destruction by immune responses.Overwhelming evidences indicate that tumors employ various mechanisms, which are required for normal cell growth, differentiation and metabolism, to evade destruction by active immune responses. For example, a portion of colorectal cancers lost MHC class I molecules to prevent recognition of tumor cells by activated T cells. Glioma , head and neck cancer secrete cytokines including TGF-beta or PGE2, which have potent suppressive activity for effector T cells. Ovarian cancers produce a large number of VEGF growth factor and CCL7 chemokine, which regulates dendritic cell differentiation and attracts...