Immunomodulatory molecules of the immune system

Cancer poses a difficult problem for immunotherapy because it arises from the host's own tissues. Many of the target antigens are tissue-specific molecules shared by cancer cells and normal cells. Thus, these are weak antigens that do not typically elicit immunity [1]. In addition, tumor cells have a number of features that make their recognition and destruction by the immune system difficult. These include the loss of expression of antigens that elicit immune responses [2], and the lack of expression of major histocompatibility (MHC) Class II and downregulation of MHC Class I expression, which can lead to non-recognition of tumors by both CD4⁺ and CD8⁺ T cells. There is typically no expression of co-stimulatory molecules, leading to inadequate activation of T cells (ignorance) and anergy [3]. Finally, tumors may evade immune recognition through more active mechanisms such as secretion of immunosuppressive cytokines [4]. Despite these obstacles, several strategies for developing effective tumor immunity have been developed. Crucial to these approaches is the discovery and understanding of the immunomodulatory molecules, particularly the co-stimulatory pathways and cytokines that are critical to the generation of an effective immune response to tumors. In this chapter, we review strategies to enhance tumor immunity through the targeting of these immunomodulatory molecules. Given the scope of the subject and ongoing research in this important field, we will focus on the some of the molecules that have been defined in more depth and refer readers to the literature for recent developments.