Two Host Factors Regulate Persistence of H7a-Specific T Cells Injected in Tumor-Bearing Mice

Background Injection of CD8 T cells primed against immunodominant minor histocompatibility antigens (MiHA) such as H7a can eradicate leukemia and solid tumors. To understand why MiHA-targeted T cells have such a potent antitumor effect it is essential to evaluate their in vivo behavior. In the present work, we therefore addressed two specific questions: what is the proliferative dynamics of H7a-specifc T cells in tumors, and do H7a-specific T cells persist long-term after adoptive transfer? Methodology/Principal Findings By day 3 after adoptive transfer, we observed a selective infiltration of melanomas by anti-H7a T cells. Over the next five days, anti-H7a T cells expanded massively in the tumor but not in the spleen. Thus, by day 8 after injection, anti-H7a T cells in the tumor had undergone more cell divisions than those in the spleen. These data strongly suggest that anti-H7a T cells proliferate preferentially and extensively in the tumors. We also found that two host factors regulated long-term persistence of anti-H7a memory T cells: thymic function and expression of H7a by host cells. On day 100, anti-H7a memory T cells were abundant in euthymic H7a-negative (B10.H7b) mice, present in low numbers in thymectomized H7a-positive (B10) hosts, and undetectable in euthymic H7a-positive recipients. Conclusions/Significance Although in general the tumor environment is not propitious to T-cell invasion and expansion, the present work shows that this limitation may be overcome by adoptive transfer of primed CD8 T cells targeted to an immunodominant MiHA (here H7a). At least in some cases, prolonged persistence of adoptively transferred T cells may be valuable for prevention of late cancer relapse in adoptive hosts. Our findings therefore suggest that it may be advantageous to target MiHAs with a restricted tissue distribution in order to promote persistence of memory T cells and thereby minimize the risk of cancer recurrence.