Begley J et al. - The authors propose that the antitumor activity of adequately stimulated tumor antigen–specific T cells is limited by local factors within the tumor milieu and that pharmacologic modulation of this milieu may overcome tumor resistance to immunotherapy. By understanding the mechanisms of cancer cell immune escape, it may be possible to design rational combinatorial approaches of novel therapies able to target immunosuppressive or antiapoptotic molecules in an attempt to reverse resistance to immune system control.