CD8+ T cell precursor frequency determines the quality of the anti-tumor immune response (40.33)

Poor clinical response to cancer vaccines may in part be due to a paucity of self-antigen specific T cells surviving negative selection. Here, we demonstrate the frequency of endogenous, mouse CD8+ T cells recognizing the melanoma/melanocyte antigen gp100 to be Curiously, treatment was impaired as the number of tumor-specific cells transferred was increased. At high doses, competition between clones significantly hindered responses. We show that tumor-specific cells primed at low precursor frequencies where competition is not operative, undergo more rounds of proliferation, acquire poly-functionality, and eradicate tumors more effectively. This work demonstrates that precursor frequency can be exploited to augment clinical vaccine strategies. Transfer of optimized numbers of naïve tumor-specific T cells, followed by in vivo activation is a new approach that should be applied to immunotherapy.