Antigen loss and tumor-mediated immunosuppression facilitate tumor recurrence.

EVALUATION OF: Jensen SM, Twitty CG, Maston LD et al. Increased frequency of suppressive regulatory T cells and T cell-mediated antigen loss results in murine melanoma recurrence. J. Immunol. 189(2), 767-776 (2012). While tumor immunotherapy has seen notable success in recent years, mechanisms that tumors utilize to escape immune responses have provided significant hurdles to maximal clinical benefit. Escape mechanisms such as antigen loss, decreased MHC expression, as well as tumor-mediated suppressive effects on antitumor immune responses, can cause the most potent antitumor immune response to be rendered powerless at the tumor site. In this study, the authors show that the adoptive transfer of tumor antigen-specific CD4(+) and CD8(+) T cells combined with tumor cell immunization can elicit regression of established subcutaneous tumors in lymphopenic, but not lymphoreplete, animals. However, using a suboptimal dose of transferred cells followed by vaccination, the authors identify the development of recurrent tumors with reduced antigen expression. These tumors could still be eradicated in similarly treated animals; however, they found that transferred CD4(+) T cells from animals with recurrent tumors acquired a suppressive phenotype. This work highlights the importance of understanding mechanisms of tumor escape, particularly underscoring the role of the tumor in modulating antigen-specific immune responses, and the critical importance of finding mechanisms to avoid the development of viable escape variants.