Antitumor Enhancement by Irradiated Haploidentical Donor Lymphocyte Infusion of Mice with Melanoma

Abstract

Background: Previous researches have reported that donor lymphocyte infusion (DLI) provides a new approach for the treatment of hematological malignancies and some solid tumors. The present study was designed to discuss the antitumor effect on mice with melanoma and possible involvement of the mechanism of haploidentical DLI in CB6F1 mice→CC3HF1 mice (F1→F1) mouse model. Methods: An F1→F1 haploidentical infusion model was established. CB6F1 mice (H-2b/d) bearing melanoma were used as recipients. CC3HF1 mice (H-2d/k) were used as donors. Changes in tumor volume and mice survival, host-derived lymphocytes proliferation, cytotoxicity, donor cell survival in vivo, histopathological examination of important organs, and the secretion Th1/Th2 cytokines were analyzed. Results: Irradiated haploidentical DLI combined with low-dose cyclophosphamide (Cy) chemotherapy induced an antitumor effect on mice with melanoma using the F1→F1 infusion model. Graft-versus-host disease (GvHD) was not obvious in any DLI-treated groups. Donor lymphocytes disappeared within 5 days after infusion, while the antitumor effect continued to be observed. Moreover, the DLI-treated groups showed a significant increase in the secretion of Th1 cytokines, including IFN-γ and IL-2, and an enhanced proliferation of CD8+ T lymphocytes and NK cells. Conclusions: Irradiated haploidentical DLI without bone marrow transplantation offers a safe, feasible, and effective approach in the treatment of melanoma.

Keywords

• Immunotherapy
• Donor lymphocytes infusion
• Mouse
• Melanoma