title: Irradiated haploidentical donor leukocyte infusions as an adoptive immunotherapy strategy to induce host-versus-tumor effects.
abstract: OBJECTIVE
  Previous research has shown that irradiated splenocytes preserve the antitumor effect and induce relatively weaker graft-versus-host disease in parent C57BL/6~CB6F1 transplantation. The present study was designed to investigate the antitumor effect of 5-Gy-irradiated haploidentical donor leukocyte infusions (DLI) without prior bone marrow transplantation and the possibly involved mechanism in (H-2d/k)~(H-2b/d) infusion model systems.
  
  
  METHODS
  Hepa 1-6 tumor-bearing mice were used to evaluate the antitumor effect and the possible mechanism of irradiated haploidentical DLI treatment. Changes in tumor volume, lymphocyte proliferation and cytotoxicity, IFN-gamma and IL-2 secretion and donor cell survival in vivo were analyzed.
  
  
  RESULTS
  After irradiated haploidentical DLI treatment of the poorly immunogeneic Hepa 1-6 tumor mouse model, the donor cells were rejected and disappeared within 4 days. Surprisingly, an antitumor response was still observed. The infusion treatment effectively inhibited tumor growth and prolonged the survival of recipients, and this effect could be enhanced by combined treatment with cyclophosphamide and impaired by deleting donor-derived T cells. Moreover, the infusion treatment increased the levels of type 1 cytokines including IFN-gamma and IL-2, and enhanced the proliferation of lymphocyte subsets, particularly CD8 + T and NK cells. Specifically, multiple infusions proved to enhance the antitumor effect without inducing graft-versus-host disease.
  
  
  CONCLUSIONS
  As an adoptive therapy, irradiated haploidentical DLI without bone marrow transplantation might be a promising and safe treatment for cancer.
authors: Department of Oncology, Union Hospital, Fujian Medical University & Fujan Key Laboratory ofTranslational Cancer Medicine, Fuzhou, PR China.
authors: Shen
authors: S
authors: Zhao
authors: Jie-yu
authors: JY
authors: Li
authors: Xiao-bin
authors: XB
authors: Zheng
authors: Feng
authors: F
authors: Peng
authors: Yun-bin
authors: YB
authors: Ye
authors: Qiang
authors: Q
authors: Chen
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000517:prevention & control; D020350:Graft vs Tumor Effect; D006239:Haplotypes; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007694:Killer Cells, Natural; D008113:Liver Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D016131:Lymphocyte Subsets; D017710:Lymphocyte Transfusion / Q000379:methods; D051379:Mice; D008815:Mice, Inbred Strains; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000528:radiation effects*; D013997:Time Factors; D014181:Transplantation Immunology; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D007376:Interleukin-2; D007371:Interferon-gamma