Th17-polarized TRP-1 cells are highly efficient in mediating the rejection of established B16 melanoma tumor upon adoptive cell transfer. (A) C57BL/6 mice B16 tumors that were sublethally irradiated (5 Gy TBI) were left untreated as controls (NT) or received adoptive transfer of 1 × 106 Th0-, Th1-, or Th17-polarized TRP-1 T cells. Th17-treated animals displayed a statistically significant greater tumor regression compared with other groups (P = .001 vs Th0- and Th1-treated groups) that were not different from NT group (P > .05). Results for tumor area are the mean of measurements from at least 5 mice per group (± SEM). Data shown are representative of multiple independent experiments. (B) Percentage of animals alive following treatment described in panel A (n = 5-7, Th1 vs Th17 P < .001). (C) C57BL/6 mice B16 tumors were sublethally irradiated and left untreated as control (NT) or received adoptive transfer of 1 × 106 Th0-, Th1-, or Th17-polarized TRP-1 T cells. In addition, mice received intravenous dose of recombinant TRP-1 vaccinia virus vaccine (rVV) immediately following cell transfer. IL-2 (36 ng/dose) was injected intraperitoneally twice daily for 3 days. Statistically significant tumor regression compared with NT group was observed in all treatment groups. The group treated with Th17 cells had a response significantly better than the Th0-treated group (P < .01), while there was no statistical difference between Th1- and Th17-injected groups (P = .175, n = 5). (D) Percentage of animals alive following treatment described in panel C (combined data from 2 independent experiments (n = 7–14, Th1 vs Th17; P < .001). (E) Animals surviving treatment with Th1 TRP-1 cells, rVV TRP-1 vaccine, and IL-2 developed less vitiligo than mice treated with Th17 TRP-1 cells, vaccination, and IL-2. Vitiligo score: 0 indicates no vitiligo (wild type); 1, depigmentation detected; 2, more than 10% vitiligo; 3, more than 25% vitiligo; 4, more than 50% vitiligo; and 5, more than 75% vitiligo. Evaluation was performed approximately 3 to 4 months after adoptive cell transfer.
