Developing cancer immunotherapies

Effective antitumor responses require communication between antigen-presenting cells, T-cell subsets, B cells and natural killer cells. However, tumors have developed a number of mechanisms to avoid detection and elimination by the immune system. This results in a microenvironment that can contribute to the failure of the immune response to the tumor or the prevention of effective immune-mediated killing. Understanding the barriers to effective tumor immunity allows for the rational design of targeted immunotherapies. The characterization of tumor antigens has led to the development of promising vaccine candidates. Our work has concentrated on the cancer/testis antigen NY-ESO-1, which has been an important focus in the development of vaccine-based therapies against melanoma. Immune responses against NY-ESO-1 can occur spontaneously or be induced by vaccination in patients with resected disease. In contrast, the use of NY-ESO-1 vaccines in the advanced melanoma setting has been disappointing, with reduced clinical and immunological efficacy. This lack of response is observed in other disease settings with other antigens, and might in part be explained by the recruitment of increased numbers of T-regulatory cells and a strong immunosuppressive environment. The benefits of cancer immunotherapy might be enhanced if it were possible to identify characteristics that distinguish patients who are more likely to respond.