DC - CIK / DC. Influence of Helicobacter pylori infection on autologous DC-CIK maintenance therapy in the advanced gastric cancer patients

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1 http / /www. biother. org Chin J Cancer Biother Feb Vol. 22 No. 1 doi /j. issn X DC - CIK Helicobacter pylori Hp dendritic cells-cytokine induced killer DC-CIK ~ Hp 45 Hp 27 / 2 DC-CIK DC DC Hp DC CD83 CD86 Hp P < HIA-DR P > Hp KPS T CD3 + CD4 + CD8 + P < CEA CA199 CA724 P < Hp T P < KPS P > Hp KPS CEA CA199 CD3 + CD4 + T Hp P < CA724 CD8 + T P > P < Hp DC CIK Hp DC-CIK R R R377 A X 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 Fujian China 2. Cancer Research Center Medical College of Xiamen University Xiamen 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 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 > 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 < but surface levels of HLA-DR in DCs had no significant difference between two groups P > In the Hp-positive group No. 10MA068 No. 3502z No. 3502z 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. 3502z No. 3502z dingyuan242007@ sina. com Chen Yuqiang corresponding author chenyq707@ 163. com http / /www. cnki. net /kcms /detail / R html

2 the quality of life KPS score and levels of T lymphocyte markers CD3 + CD4 + and CD8 + were significantly increased P < but levels of tumor markers CEA CA199 and CA724 were significantly decreased P < after treatment. In the Hp-negative group levels of tumor markers and the T lymphocyte markers were significantly different before and after treatment P < but the KPS score was not significantly improved P > 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 < In contrast the two groups did not significantly differ in tumor stability CA724 expression and the number of CD8 + T cells P > At the end of 2-years follow-up the median survival time was months in the HP-positive group and months in the HP-negative group P < 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 SJB01 rhtnf-α % 1 2 / Sigma P11- Helicobacter pylori Hp rhil-4 SJB02-2 rhil- Hp CD3 SB- JM0112 Hp CD CD dendritic HLA-DR 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 = Sex Male ~ Age t /a DC-CIK 4 > 3 KPS > 60 AJCC stages Ⅲa Ⅲb 12 7 Ⅳ Hp 2 ~ Ficoll CEDARLANE SJA03 -γ IFN-γ SJC02 Female < Surgery cm 1 5 min CL DC-CIK rhgm-csf SJA

3 . DC-CIK 69 RPMI U /ml CEA CA199 CA724 T CD3 + CD4 + CD8 + CD4 + /CD DC CIK 1. 8 Hp Hp 50 ml SPSS14. 0 x 珋 ± s t P < P < ~ /ml GM-CSF IL-4 TNF-α DC IFN-γ CD3 IL- 2 CIK Hp Hp DC 0. 1 mg /ml DC 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 Version DC-CIK 1 DC-CIK 2 12 d 16 d 0 1 ~ DC 1 ml ml 1 /d CIK 100 ml /d Hp + Hp - DC Fig. 1 Morphological change of DCs during the maturation process in Hp + and Hp - groups Karnovfsky performance status KPS DC DC DC CT /MRI /PET-CT CD83 CD86 HLA-DR 4 response evaluation criteria in 2 Hp DC CD83 CD86 solid tumor RECISI T DC 4 h TNF-α 1 5 Hp Hp P < 0. 05

4 HLA-DR P > Hp Hp mdc % P < KPS Tab. 2 Expression of surface marker molecules P < on mdc in Hp + and Hp - groups % Group CD83 CD86 HLA-DR Hp ± ± ± Hp ± * ± * ± * * P < vs Hp - agent group 2. 3 DC-CIK Hp P < Hp KPS ± CEA CA199 P < CA vs ± 5. 94P = P = DC-CIK Hp KPS ± P = Hp KPS ± Hp PR 2 SD 18 PD 7 74% 20 / 27 Hp PR 5 SD 30 PD % 35 /45 P = CEA CA199 CA724 P > 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 ± ± ± Post-treatment ± * ± * ± * Hp + Pre-treatment ± ± ± Post-treatment ± ** ± ** ± ** * P < ** P < vs pre-treatment in the same group P < vs post-treatment in the Hp - group CD4 + /CD8 + 4 T P < Hp CD3 + P > DC-CIK CD3 + CD8 + T CD4 + /CD8 + CD4 + T CD8 + T P > CD4 + T Hp P < 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 ± ± ± ± Post-treatment ± * ± * ± ** ± ** Hp + Pre-treatment ± ± ± ± Post-treatment ± ** ± ** ± * ± ** * P < ** P < vs pre-treatment in the same group P < vs post-treatment in the Hp - group

5 . DC-CIK Th1 Tanaka 18 Cag CIK A + DC CD86 Cag A VacA DC mg Hp DC DC Hp Hp median survival time MST Hp MST MST P = Hp Hp CD8 + Hp Hp 5 DC T 6 MHC-Ⅱ CD4 + T Ⅰ 7 Hp Hp 58% 74% CEA 63. 4% Hp 8 Hp P < Hp P > Hp 2 Hp MST Hp MST Hp DC Hp Hp D2 protein kinase D2 PKD2 10 Hp Hp DC Kranzer 16 Hp DC immature DC idc Hp DC CD80 CD83 CD86 HLA-DR Hafsi 17 Hp DC idc DC Hp DC CD83 CD86 Hp HLA-DR DC Hp T CD3 + CD4 + CD4 + / CA19-9 CA724 P < Hp Knon 20 HER-2 DC 9 / -1 apurinic /apyrimdinic endonuclease-1 APE helicobacter CEA CA19-9 pylori heat shock protein 60 HPHSP60 12 DC-CIK 1 DC-CIK Hp DC T DC DC DC DC DC 1. Meta J Gonzalez CA Agudo A. Carcinogenesis prevention and early detection of gastric cancer Where we are and where we should go J. Int J Cancer Kano Y Wang XJ Junko S et al. Pharmacological properties of galenical prepration XXH Pharmacokinetics study of 6 7-dim-

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