Genetic Polymorphism and Tumor Immunotherapy

Numerous immunotherapeutic strategies have been tested over the last decade but their success, especially against cancer, has been both varied and unpredictable. Gene polymorphisms in key immunoregulatory molecules may contribute to the heterogeneity in outcome between individuals receiving the same immunotherapeutic treatment. Typically, active cancer immunotherapy aims to redirect or modulate the function of antigen presenting cells (APCs), especially dendritc cells (DCs) that play a critical role in both innate and adaptive immune responses. This includes enhancing the function of APCs by promoting the growth and differentiation of DCs, potentiating T cell activation by improving costimulation and engineering vaccine vectors to significantly enhance the immunogenicity of vaccinogens. Several groups have investigated the functional consequences of polymorphisms in key immunoregulatory moleculesincluding antigen presenting molecules, cytokines and chemokines and their receptors, adhesion and costimulatory molecules, toll-like receptors and intracellular signaling molecules that play a vital role in antigen recognition and the control of adaptive immune responses. This review examines both genetic polymorphisms in these immunoregulatory molecules and their relationship to immunotherapeutic outcome, especially against carcinoma. (175 words)