http / /www. biother. org Chin J Cancer Biother Feb. 2015 Vol. 22 No. 1 doi 10. 3872 /j. issn. 1007-385X. 2015. 01. 012 67 DC - CIK 1 1 1 1 2 1 1. 174 361003 2. 361000 Helicobacter pylori Hp dendritic cells-cytokine induced killer DC-CIK 2010 6 2012 6 174 72 29 ~ 90 56 Hp 45 Hp 27 / 2 DC-CIK DC DC Hp DC CD83 CD86 Hp P < 0. 01 HIA-DR P > 0. 05 Hp KPS T CD3 + CD4 + CD8 + P < 0. 05 CEA CA199 CA724 P < 0. 05 Hp T P < 0. 05 KPS P > 0. 05 Hp KPS CEA CA199 CD3 + CD4 + T Hp P < 0. 05 CA724 CD8 + T P > 0. 05 2 12. 64 11. 42 P < 0. 05 Hp DC CIK Hp DC-CIK R735. 2 R730. 54 R377 A 1007-385X 2015 01-0067-06 Influence of Helicobacter pylori infection on autologous DC-CIK maintenance therapy in the advanced gastric cancer patients Ding Yuan 1 Chen Yuqiang 1 Li Qiaozhen 1 Mi YanJun 1 Yan Jianghua 2 Ye Yanhua 1 1. Department of Oncology No. 174 Hospital of PLA Xiamen 361003 Fujian China 2. Cancer Research Center Medical College of Xiamen University Xiamen 361005 Fujian China Abstract Objective To evaluate the effect of Helicobacter pylori Hp infection on the outcome of maintenance therapy with autologous dendritic cells-cytokine induced killer DC-CIK cells in gastric cancer patients. Methods Seventytwo patients with advanced gastric cancer aged 29-90 years who were admitted to the Department of Oncology of No. 174 Hospital of PLA between June 2010 and June 2012 were included in this study. Based on the gastroscopic findings patients were divided into two groups Hp-positive and Hp-negative. Both groups received two courses of autologous DC-CIK immunotherapy after surgery or radiotherapy and chemotherapy. At the end of treatment DC differentiation and maturation treatment efficacy and patients outcomes in the two groups were analyzed. Results No significant difference was observed in the morphology and maturation status of DCs between two groups P > 0. 05. Levels of CD83 and CD86 on the surface of DCs were significantly higher in the Hp-positive group than those in the Hp-negative group P < 0. 01 but surface levels of HLA-DR in DCs had no significant difference between two groups P > 0. 05. In the Hp-positive group No. 10MA068 No. 3502z20134026 No. 3502z20144034 Project supported by the Medical Science and Technology Innovation Subject of Nanjing Military Region No. 10MA068 and the Science and Technology Innovation Project of Xiamen City No. 3502z20134026 No. 3502z20144034 1983- E-mail dingyuan242007@ sina. com Chen Yuqiang corresponding author E-mail chenyq707@ 163. com http / /www. cnki. net /kcms /detail /31. 1725. R. 20150205. 1444. 008. html
68 2015 2 22 1 the quality of life KPS score and levels of T lymphocyte markers CD3 + CD4 + and CD8 + were significantly increased P < 0. 05 but levels of tumor markers CEA CA199 and CA724 were significantly decreased P < 0. 05 after treatment. In the Hp-negative group levels of tumor markers and the T lymphocyte markers were significantly different before and after treatment P < 0. 05 but the KPS score was not significantly improved P > 0. 05. Hp-positive patients had better KPS score higher levels of CEA and CA199 and more abundant CD3 + CD4 + T cells than Hp-negative patients P < 0. 05. In contrast the two groups did not significantly differ in tumor stability CA724 expression and the number of CD8 + T cells P > 0. 05. At the end of 2-years follow-up the median survival time was 12. 64 months in the HP-positive group and 11. 42 months in the HP-negative group P < 0. 05. Conclusion Hp infection may help stabilize the tumor size improve the quality of life and prolong the survival time in patients with advanced gastric cancer undergoing maintenance therapy with DC-CIK cells. Key words dendritic cells-cytokine induced killer DC-CIK cell Helicobacter pylori gastric cancer Chin J Cancer Biother 2015 22 1 67-72 2 SJB01 rhtnf-α 74. 37% 1 2 / Sigma P11- Helicobacter pylori Hp rhil-4 SJB02-2 rhil- Hp CD3 SB- JM0112 Hp CD-83 11-0839 CD-86 53-0869 dendritic HLA-DR 12-9956 Bioscience cell DC cytokine in- duced killer CIK 1 Tab. 1 Clinical features of the patients with gastric cancer 1 HP + Hp - Features P 1. 1 n = 45 n = 27 2010 6 2012 6 Sex 174 72 Male 29 15 0. 454 44 28 29 ~ 90 56 Age t /a 56 26 19 0. 285 DC-CIK 4 > 3 KPS > 60 AJCC stages Ⅲa 17 14 0. 234 Ⅲb 12 7 Ⅳ 16 6 1 1. 3 Hp 2 ~ 5 1. 2 010 Ficoll CEDARLANE SJA03 -γ IFN-γ SJC02 Female 16 12 < 56 19 8 Surgery 28 16 0. 803 cm 1 5 min CL5020-1. 4 DC-CIK rhgm-csf SJA01-4 1. 4. 1
. DC-CIK 69 RPMI 1640 20 U /ml CEA CA199 CA724 T - 20 3 CD3 + CD4 + CD8 + CD4 + /CD8 + 1. 4. 2 DC CIK 1. 8 Hp Hp 50 ml SPSS14. 0 x 珋 ± s t P < 0. 05 P < 1 10 6 ~ 2 10 6 /ml GM-CSF IL-4 TNF-α DC IFN-γ CD3 IL- 2 CIK 5 2. 1 Hp Hp DC 0. 1 mg /ml DC 8 24 48 72 h DC 3 DC 9 CIK 100 ml 1. 5 DC Hp DC 100 μl5 1 4 PE-CD86 20 μl 8 DC DC FITC-CD83 20 μl PE-HLA-DR 5 μl 4 30 min PBS 4% 15 min PBS 1 ml PBS DC CD83 CD86 HLA-DR WinMDI Version2. 9 1. 6 DC-CIK 1 DC-CIK 2 12 d 16 d 0 1 ~ 7 8 9 10 11 12 DC 1 ml 1 10 6 0. 25 ml 1 /d 9 10 11 12 CIK 100 ml 1 10 9 1 /d 1. 7 1 Hp + Hp - DC 400 1. 7. 1 2 Fig. 1 Morphological change of DCs during the maturation process in Hp + and Hp - groups 400 1. 7. 2 Karnovfsky performance status KPS 3 2. 2 DC 1. 7. 3 2 8 DC DC CT /MRI /PET-CT CD83 CD86 HLA-DR 4 response evaluation criteria in 2 Hp DC CD83 CD86 solid tumor RECISI 1. 7. 4 T 0. 01 2 3 1 DC 4 h TNF-α 1 5 Hp Hp P < 0. 05
70 2015 2 22 1 HLA-DR P > 0. 05 2 Hp Hp mdc % P < 0. 01 KPS Tab. 2 Expression of surface marker molecules P < 0. 05 on mdc in Hp + and Hp - groups % Group CD83 CD86 HLA-DR Hp - 62. 13 ± 3. 81 67. 13 ± 3. 70 81. 91 ± 4. 22 Hp + 68. 96 ± 3. 94 * 76. 01 ± 3. 95 * 83. 05 ± 3. 98 * * P < 0. 05 vs Hp - agent group 2. 3 DC-CIK 2. 3. 1 Hp P < 0. 05 Hp KPS 78. 67 ± CEA CA199 P < 0. 05 CA724 6. 40 vs 79. 33 ± 5. 94P = 0. 138 2 P = 0. 091 DC-CIK Hp KPS 80. 67 ± 5. 94 P = 0. 167 Hp KPS 86. 67 ± 4. 88 2. 3. 2 Hp PR 2 SD 18 PD 7 74% 20 / 27 Hp PR 5 SD 30 PD 10 77. 8% 35 /45 P = 0. 274 3 CEA CA199 CA724 P > 0. 05 CEA CA199 CA724 3 Hp Hp DC-CIK ρ B / ng ml - 1 Tab. 3 Expression of the tumor markers between Hp + and Hp - groups before and after DC-CIK treatment ρ B / ng ml - 1 Hp - Group CEA CA199 CA724 Pre-treatment 42. 353 ± 17. 792 60. 080 ± 32. 850 43. 148 ± 26. 108 Post-treatment 36. 61 ± 17. 229 * 52. 015 ± 29. 033 * 37. 177 ± 21. 741 * Hp + Pre-treatment 41. 385 ± 16. 786 56. 958 ± 36. 076 42. 738 ± 29. 880 Post-treatment 29. 443 ± 15. 444 ** 43. 388 ± 24. 925 ** 28. 835 ± 19. 068 ** * P < 0. 05 ** P < 0. 01 vs pre-treatment in the same group P < 0. 05 vs post-treatment in the Hp - group 2. 3. 3 CD4 + /CD8 + 4 T P < 0. 05 Hp CD3 + P > 0. 05 2 DC-CIK CD3 + CD8 + T CD4 + /CD8 + CD4 + T CD8 + T P > 0. 05 CD4 + T Hp P < 0. 05 Hp - 4 Hp Hp DC-CIK T % Tab. 4 Expression of T cell subset in Hp + and Hp - patients before and after DC-CIK treatment % Group CD3 + CD4 + CD8 + CD4 + /CD8 + Pre-treatment 56. 934 ± 8. 811 29. 519 ± 9. 339 27. 116 ± 7. 199 1. 173 ± 0. 560 Post-treatment 60. 279 ± 9. 883 * 31. 795 ± 9. 899 * 24. 484 ± 6. 226 ** 1. 425 ± 0. 696 ** Hp + Pre-treatment 57. 092 ± 7. 998 29. 708 ± 8. 635 27. 105 ± 7. 827 1. 195 ± 0. 626 Post-treatment 64. 288 ± 8. 849 ** 36. 175 ± 8. 875 ** 25. 374 ± 7. 376 * 1. 543 ± 0. 622 ** * P < 0. 05 ** P < 0. 01 vs pre-treatment in the same group P < 0. 05 vs post-treatment in the Hp - group
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