Both hematopoietic and nonhematopoietic host cells are required for the antirecurrence/metastases effect of anti-CD137 mAb. (A) A schematic of the mouse model for melanoma recurrence/metastases after bone marrow (BM) reconstitution and anti-CD137 mAb treatment. At day −90, indicated recipient mice were irradiated with 650 Gy twice on the same day. BM cells were harvested from the indicated donor mice and transferred at 5 × 106/mouse into indicated recipient mice. The percentage of bone marrow chimerism was evaluated 30 days after BM transplantation. Chimeric mice were inoculated with 2 × 105 B16-OVA tumor cells subcutaneously at day −50. Ten days later, tumor nodules were surgically resected. Mice rested for 1 month to facilitate the development of memory T cells and were subsequently treated with anti-CD137 mAb twice as indicated. At day 0, mice were rechallenged with B16-OVA tumor cells at 2 × 105 subcutaneously or intravenously. (B) BM-reconstituted and tumor-resected mice were treated with control rat Ig or anti-CD137 mAb (left panel) or control rat Ig (right panel), and B16-OVA tumor cells were inoculated subcutaneously 1 week later. Each point indicates the mean tumor diameters in a group of 5 mice, and error bars show SD. *P < .05, **P < .01 compared with Thy1.2BM/Thy1.1 host treated with control rat Ig. +P < .05, ++P < .01 compared with Thy1.2BM/Thy1.1 host treated with anti-CD137 mAb.
