title: [Anti-tumor effect of cisplatin combined with DC vaccine on tumor-bearing mice].
abstract: OBJECTIVE
  To explore the anti-tumor mechanism of the combination of cisplatin with DC vaccine in tumor-bearing mice.
  
  
  METHODS
  B16 melanoma cells were treated with cisplatin at the final concentration of 20 µg/ml in vitro for 24 h. The expression of HMGB1, Hsp70 and TGF-β were detected by Western blot. B16 tumor-bearing mouse models were generated. The therapeutic effect of the combination of cisplatin (100 µg/mouse i.p., for sequential 3 days) and intratumoral injection of DC cells (3×10(6)/mouse, twice with a 7-day interval) in the tumor-bearing mouse models was evaluated. Expression of MHC II, ICAM-1 and CD86 was analyzed by flow cytometry. The mice were sacrificed at 28 days after tumor cell inoculation. The tumors were removed and weighed, and tissue samples were taken for pathological examination. Tumor infiltrating lymphocytes (TIL) were isolated by discontinuous gradient centrifugation. The distribution of T-reg and CD8(+) T cells in the TIL was analyzed by flow cytometry, and the ratio of CD8(+) T/T-reg was determined. The activity of cytotoxic lymphocytes (CTL) was determined by microcytotoxicity assay.
  
  
  RESULTS
  Cisplatin enhanced both the B16 cell apoptosis and HMGB1 expression. After loading with cisplatin-treated cell lysate, the expression of MHC II, ICAM-1 and CD86 on DC cells were (47.5 ± 8.8)%, (35.5 ± 8.3)% and (36.2 ± 9.2)%, respectively. At 28 days after tumor cell inoculation, the tumor weight of the control group was (2.1 ± 0.6) g, that of the cisplatin group was (0.3 ± 0.2) g and that of cisplatin + DC vaccine group was (0.5 ± 0.2) g, showing a significant inhibition of tumor growth (P < 0.01). Furthermore, the CD8(+) T/T-reg ratio and CTL activity in TIL were also significantly enhanced in the tumor-bearing mice treated with cisplatin + DC vaccine. When the effector-to-target ratio was 20:1, 10:1 and 5:1, the CTL activity in the cisplatin + DC vaccine treated mice was (25.0 ± 5.0)%, (22.0 ± 6.0)% and (14.0 ± 4.0)%, respectively, significantly higher than (8.2 ± 3.6)%, (6.7 ± 1.8)% and (3.6 ± 1.9)%, respectively, in the control group (all P < 0.01).
  
  
  CONCLUSIONS
  Cisplatin promotes the anti-tumor effect of DC vaccine by down-regulating T-reg cells and enhancing the CTL activity in tumors.
authors.affiliation: Department of Molecular Biology, Hebei Medical University, Shijiazhuang, China.
authors.forename: Hong-yu
authors.initials: HY
authors.lastname: You
authors.forename: Wei-guang
authors.initials: WG
authors.lastname: Lian
authors.forename: Huan-ling
authors.initials: HL
authors.lastname: Zhang
authors.forename: Jun-xia
authors.initials: JX
authors.lastname: Wang
authors.forename: Kai-xia
authors.initials: KX
authors.lastname: Zhang
authors.forename: Shu-xia
authors.initials: SX
authors.lastname: Song
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051940:B7-2 Antigen / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D019496:Cancer Vaccines / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005802:Genes, MHC Class II; D024243:HMGB1 Protein / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D051940:B7-2 Antigen; D019496:Cancer Vaccines; D024243:HMGB1 Protein; D018799:Intercellular Adhesion Molecule-1; D002945:Cisplatin