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

Abstract

Here we investigate the minimal requirements for induction of an anti-tumor response in CD8 T cells in vivo. We compare the efficacy of adoptive transfer of CD8 T cells with a transgenic TCR specific for the main cytotoxic T lymphocyte epitope of the influenza virus nucleoprotein (NP) on the growth of NP-expressing EL4 tumors under different conditions. In a setting in which tumor rejection is solely dependent on tumor-specific CD8 T cells, small immunogenic 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 the tumor bed. Nevertheless, tumor rejection does not occur. In sharp contrast, the same immunogenic 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 large tumor mass from the response to a small tumor is that, in the latter case, activated CD8 T cells appear much later, and in much smaller numbers. Efficacy of adoptive transfer is thus dictated by the size of the tumor mass at the time of transfer. These findings predict that treatment of minimal residual disease with adoptive transfer will fail, unless vaccination is also provided at the time of transfer.