Tumor size at the time of adoptive transfer determines whether tumor rejection occurs

. We compare the efficacy of adoptive transfer of CD8 T cells with a transgenicTCR specific for the main cytotoxic T lymphocyte epitope of the influenza virus nucleopro-tein (NP) on the growth of NP-expressing EL4 tumors under different conditions. In a settingin which tumor rejection is solely dependent on tumor-specific CD8 T cells, small immuno-genic tumors fail to induce a rejection response, despite the fact that they are not ignored:tumor-specific CD8 T cells are activated, differentiate into effector cells and infiltrate thetumor bed. Nevertheless, tumor rejection does not occur. In sharp contrast, the same immu-nogenic tumor, when growing as a large tumor mass, is rejected by transferred tumor-specific CD8 T cells. The main features which distinguish the rejection response to a largetumor mass from the response to a small tumor is that, in the latter case, activated CD8 Tcells appear much later, and in much smaller numbers. Efficacy of adoptive transfer is thusdictated by the size of the tumor mass at the time of transfer. These findings predict thattreatment of minimal residual disease with adoptive transfer will fail, unless vaccination isalso provided at the time of transfer.