Interleukin-21 restrains tumor growth and induces a substantial increase in the number of circulating tumor-specific T cells in a murine model of malignant melanoma

Abstract

New strategies of immunotherapy are currently being evaluated, and the combination of chemo- and immunotherapy has shown promising results. The cytokine interleukin-21 (IL-21) is known to enhance immune function, and in this study we have investigated its ability to boost the efficacy of chemoimmunotherapy-cyclophosphamide and adoptive cell transfer (ACT)-in the B16-OVA/OT-I murine model of malignant melanoma. Subcutaneous B16-OVA tumors were established in C57BL/6J mice 8 days before adoptive transfer of tumor-specific OT-I T cells. In addition to cyclophosphamide and ACT, one group of mice received daily injections of murine IL-21 (mIL-21). Mice treated with mIL-21 had more tumor-specific T cells in the circulation 4 and 7 days following ACT (P=0.004 and P=0.002, respectively). Importantly, mIL-21 and ACT controlled tumor growth instantly and more effectively than ACT alone (P=0.001, day 4)-an effect that persisted up to 5 days after the last mIL-21 injection. We conclude that mIL-21 enhances chemoimmunotherapy: it amplifies the number of tumor-specific T cells in the circulation and also stunts early tumor growth.