Due to genetic instability, cancer cells readily develop heritable variants that escape destruction or growth arrest. For example, solid tumors 1cm in diameter (~10⁹ cancer cells) commonly contain variant cancer cells that can no longer be killed by T cells directly because of loss of antigen, MHC class I down-regulation, or antigen mutation. Stromal cells within tumors are genetically much more stable and can cross-present tumor-specific antigens released from cancer cells as targets for T cells. Zhang and colleagues demonstrate that a single transfer of T cells targeting only antigen-loaded stromal cells (cancer cells lacked the presenting MHC molecule) caused long-term equilibrium between host and cancer. Untreated tumors (a), shown here on day 20, killed mice within a month and consisted of a homogenous, well-vascularized mass of rapidly proliferating cancer cells with little evidence of apoptosis or necrosis. In contrast, T-cell–treated tumors (b) became necrotic with only a rim of viable, mitotic cancer cells adjacent to lymphocytes and pre-existing vasculature. These tumors persisted for months, shown here at day 70. Tumor eradication is obviously preferable to tumor arrest; however, for many aggressively growing, rapidly lethal cancers, long-term arrest of growth with equilibrium between the host and cancer would be an acceptable goal. Therefore, targeting stromal cells that cross-present antigens released from cancer cells may prove to become an important new approach to cancer therapy. For details, see the article by Zhang and colleagues on page 1563 of this issue.