Analysis of clinical efficacy of dendritic cells-cytokine induced killer cells adoptive immunotherapy combined with chemotherapy for patients with gastric cancer after radical gastrectomy_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHU Xiaoliang ^1,2 , ZHANG Zhengcong ² , WANG Haiping ³ , LÜ Pengfei ² , YUAN Defeng ² , DING Fanghui ¹ , WANG Mingfei ¹ , MENG Wenbo ⁴ , ZHANG Lei ¹ , ZHU Kexiang ⁵ , MIAO Long ⁵ , BAI Xiaoping ² , ZHANG Jianjun ³ ,  LI Xun ^1,3

1. The Fifth Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, P. R. China;
2. Department of General Surgery, Donggang District, The First Hospital of Lanzhou University, Lanzhou 730000, P. R. China;
3. Gansu Provincial Key Laboratory of Biotherapy and Regenerative Medicine, Lanzhou 730000, P. R. China;
4. Department of Special Minimally Invasive Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, P. R. China;
5. The Second Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, P. R China;

Corresponding author：

LI Xun, Email: lxdr21@126.com

Keywords：

gastric cancer; dendritic cell; cytokine-induced killer cell; adoptive immunotherapy; chemotherapy

DOI：

10.7507/1007-9424.201910061

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the safety and clinical efficacy of dendritic cell (DC)-cytokine induced killer (CIK) cell adoptive immunotherapy combined with chemotherapy in patients with gastric cancer after radical gastrectomy.Methods Forty-eight patients with gastric cancer after the radical gastrectomy receiving the DC-CIK cell adoptive immunotherapy combined with XELOX or FOLFOX chemotherapy were enrolled as a study group in the First Hospital of Lanzhou University from January 2014 to January 2016. In addition, 48 patients with gastric cancer after the radical gastrectomy in the same period and only receiving XELOX or FOLFOX chemotherapy were collected as a control group. The CD3⁺, CD3⁺CD4⁺, CD3⁺CD8⁺, CD3^–CD56⁺ (NK cell), and CD3⁺CD56⁺ (NKT cell), toxic reaction, quality of life were evaluated in both groups before and after the treatment, and the long term effect were compared in both groups.Results ① There were no significant differences in the gender, age, clinical stage, etc. between the two groups (P>0.05). ② The CD3⁺, CD3⁺CD4⁺, CD3⁺CD8⁺, CD3^–CD56⁺, and CD3⁺CD56⁺ cells in the peripheral blood had no significant changes between before and after treatment in the study group (P>0.05), which were decreased after the treatment in the control group as compared with before the treatment and were significantly lower than those in the study group (P<0.05). ③ The levels of CEA, CA19-9, and CA724 in the peripheral blood after the treatment in the study group and the control group were significantly lower than those before the treatment (P<0.05), which in the study group were significantly lower than those in the control group after the treatment (P<0.05). ④ The incidences of leukopenia, thrombocytopenia, and diarrhea in the study group were significantly lower than those in the control group (P<0.05). ⑤ Compared with before the treatment, the body function and emotional function after the treatment were significantly improved in the study group (P<0.05). And in the body function, emotion function, role function, cognitive function, and social function were significantly improved than those in the control group (P<0.05) after the treatment. ⑥ The progression-free survival in the study group was significantly better than that in the control group (P<0.05). There was no significant difference in the overall survival between the study group and the control group (P>0.05).Conclusion DC-CIK cell adoptive immunotherapy combined with chemotherapy could significantly improve immune status and quality of life of patients with gastric cancer after radical gastrectomy, reduce adverse effects of chemotherapy, improve long term effect, and prolong progression-free survival.

Citation： ZHU Xiaoliang, ZHANG Zhengcong, WANG Haiping, LÜ Pengfei, YUAN Defeng, DING Fanghui, WANG Mingfei, MENG Wenbo, ZHANG Lei, ZHU Kexiang, MIAO Long, BAI Xiaoping, ZHANG Jianjun, LI Xun. Analysis of clinical efficacy of dendritic cells-cytokine induced killer cells adoptive immunotherapy combined with chemotherapy for patients with gastric cancer after radical gastrectomy. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2020, 27(7): 801-807. doi: 10.7507/1007-9424.201910061 Copy

1.	Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2.	Chen W, Sun K, Zheng R, et al. Cancer incidence and mortality in China, 2014. Chin J Cancer Res, 2018, 30(1): 1-12.
3.	Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin, 2015, 65(2): 87-108.
4.	Anguille S, Smits EL, Lion E, et al. Clinical use of dendritic cells for cancer therapy. Lancet Oncol, 2014, 15(7): e257-e267.
5.	Ilett EJ, Prestwich RJ, Melcher AA. The evolving role of dendritic cells in cancer therapy. Expert Opin Biol Ther, 2010, 10(3): 369-379.
6.	Jäkel CE, Vogt A, Gonzalez-Carmona MA, et al. Clinical studies applying cytokine-induced killer cells for the treatment of gastrointestinal tumors. J Immunol Res, 2014, 2014: 897214.
7.	Gungor-Ordueri NE, Tang EI, Celik-Ozenci C, et al. Ezrin is an actin binding protein that regulates sertoli cell and spermatid adhesion during spermatogenesis. Endocrinology, 2014, 155(10): 3981-3995.
8.	Di L, Zhu Y, Jia J, et al. Clinical safety of induced CTL infusion through recombinant adeno-associated virus-transfected dendritic cell vaccination in Chinese cancer patients. Clin Transl Oncol, 2012, 14(9): 675-681.
9.	Montagna D, Turin I, Schiavo R, et al. Feasibility and safety of adoptive immunotherapy with ex vivo-generated autologous, cytotoxic T lymphocytes in patients with solid tumor. Cytotherapy, 2012, 14(1): 80-90.
10.	Amin MB, Edge SB, Greene FL, et al. AJCC Cancer Staging Manual. 8th ed. NewYork: Springer, 2017.
11.	中华人民共和国卫生部医政司. 胃癌诊疗规范(2011 年版). 中国医学前沿杂志(电子版), 2012, 4(5): 62-71.
12.	高作文, 郑劼, 娄金书, 等. DC-CIK 细胞免疫治疗胃癌的临床疗效及预后分析. 中国肿瘤生物治疗杂志, 2017, 24(2): 174-179.
13.	万崇华, 陈明清, 张灿珍, 等. 癌症患者生命质量测定量表EORTC QLQ-C30中文版评介. 实用肿瘤杂志, 2005, 20(4): 353-355.
14.	杨林, 刘静维, 张雯, 等. DC-CIK 细胞联合化疗治疗局部晚期不可切除或转移性胃腺癌的临床疗效. 中国肿瘤生物治疗杂志, 2017, 24(9): 966-971.
15.	Couzin-Frankel J. Breakthrough of the year 2013. Cancer immunotherapy. Science, 2013, 342(6165): 1432-1433.
16.	Galluzzi L, Senovilla L, Vacchelli E, et al. Trial watch: Dendritic cell-based interventions for cancer therapy. Oncoimmunology, 2012, 1(7): 1111-1134.
17.	Verma V, Kim Y, Lee MC, et al. Activated dendritic cells delivered in tissue compatible biomatrices induce in-situ anti-tumor CTL responses leading to tumor regression. Oncotarget, 2016, 7(26): 39894-39906.
18.	吴凤丽, 李国华. 树突状细胞疫苗在胃癌免疫治疗中的研究进展. 世界华人消化杂志, 2014, 22(1): 46-52.
19.	Thanendrarajan S, Nowak M, Abken H, et al. Combining cytokine-induced killer cells with vaccination in cancer immunotherapy: more than one plus one? Leuk Res, 2011, 35(9): 1136-1142.
20.	龚福生, 陈路川, 杨建伟, 等. 自体肿瘤抗原负载 DC-CIK 细胞治疗胃癌的疗效分析. 中国肿瘤生物治疗杂志, 2016, 23(6): 813-818.
21.	刘小军, 侯小明, 张健, 等. 自体 DC-CIK 细胞联合化疗治疗晚期胃癌的回顾性研究. 中国肿瘤生物治疗杂志, 2016, 23(6): 819-823.
22.	刘清池, 张慧敏, 张玉娜, 等. DC-CIK 细胞清除微小残留白血病的临床研究. 中国肿瘤生物治疗杂志, 2013, 20(4): 398-403.
23.	Lee JH, Lee JH, Lim YS, et al. Adjuvant immunotherapy with autologous cytokine-induced killer cells for hepatocellular carcinoma. Gastroenterology, 2015, 148(7): 1383-1391.
24.	Liu L, Zhang W, Qi X, et al. Randomized study of autologous cytokine-induced killer cell immunotherapy in metastatic renal carcinoma. Clin Cancer Res, 2012, 18(6): 1751-1759.
25.	Pan K, Guan XX, Li YQ, et al. Clinical activity of adjuvant cytokine-induced killer cell immunotherapy in patients with post-mastectomy triple-negative breast cancer. Clin Cancer Res, 2014, 20(11): 3003-3011.
26.	Leemhuis T, Wells S, Scheffold C, et al. A phase Ⅰ trial of autologous cytokine-induced killer cells for the treatment of relapsed Hodgkin disease and non-Hodgkin lymphoma. Biol Blood Marrow Transplant, 2005, 11(3): 181-187.

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2. Chen W, Sun K, Zheng R, et al. Cancer incidence and mortality in China, 2014. Chin J Cancer Res, 2018, 30(1): 1-12.
3. Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin, 2015, 65(2): 87-108.
4. Anguille S, Smits EL, Lion E, et al. Clinical use of dendritic cells for cancer therapy. Lancet Oncol, 2014, 15(7): e257-e267.
5. Ilett EJ, Prestwich RJ, Melcher AA. The evolving role of dendritic cells in cancer therapy. Expert Opin Biol Ther, 2010, 10(3): 369-379.
6. Jäkel CE, Vogt A, Gonzalez-Carmona MA, et al. Clinical studies applying cytokine-induced killer cells for the treatment of gastrointestinal tumors. J Immunol Res, 2014, 2014: 897214.
7. Gungor-Ordueri NE, Tang EI, Celik-Ozenci C, et al. Ezrin is an actin binding protein that regulates sertoli cell and spermatid adhesion during spermatogenesis. Endocrinology, 2014, 155(10): 3981-3995.
8. Di L, Zhu Y, Jia J, et al. Clinical safety of induced CTL infusion through recombinant adeno-associated virus-transfected dendritic cell vaccination in Chinese cancer patients. Clin Transl Oncol, 2012, 14(9): 675-681.
9. Montagna D, Turin I, Schiavo R, et al. Feasibility and safety of adoptive immunotherapy with ex vivo-generated autologous, cytotoxic T lymphocytes in patients with solid tumor. Cytotherapy, 2012, 14(1): 80-90.
10. Amin MB, Edge SB, Greene FL, et al. AJCC Cancer Staging Manual. 8th ed. NewYork: Springer, 2017.
11. 中华人民共和国卫生部医政司. 胃癌诊疗规范(2011 年版). 中国医学前沿杂志(电子版), 2012, 4(5): 62-71.
12. 高作文, 郑劼, 娄金书, 等. DC-CIK 细胞免疫治疗胃癌的临床疗效及预后分析. 中国肿瘤生物治疗杂志, 2017, 24(2): 174-179.
13. 万崇华, 陈明清, 张灿珍, 等. 癌症患者生命质量测定量表EORTC QLQ-C30中文版评介. 实用肿瘤杂志, 2005, 20(4): 353-355.
14. 杨林, 刘静维, 张雯, 等. DC-CIK 细胞联合化疗治疗局部晚期不可切除或转移性胃腺癌的临床疗效. 中国肿瘤生物治疗杂志, 2017, 24(9): 966-971.
15. Couzin-Frankel J. Breakthrough of the year 2013. Cancer immunotherapy. Science, 2013, 342(6165): 1432-1433.
16. Galluzzi L, Senovilla L, Vacchelli E, et al. Trial watch: Dendritic cell-based interventions for cancer therapy. Oncoimmunology, 2012, 1(7): 1111-1134.
17. Verma V, Kim Y, Lee MC, et al. Activated dendritic cells delivered in tissue compatible biomatrices induce in-situ anti-tumor CTL responses leading to tumor regression. Oncotarget, 2016, 7(26): 39894-39906.
18. 吴凤丽, 李国华. 树突状细胞疫苗在胃癌免疫治疗中的研究进展. 世界华人消化杂志, 2014, 22(1): 46-52.
19. Thanendrarajan S, Nowak M, Abken H, et al. Combining cytokine-induced killer cells with vaccination in cancer immunotherapy: more than one plus one? Leuk Res, 2011, 35(9): 1136-1142.
20. 龚福生, 陈路川, 杨建伟, 等. 自体肿瘤抗原负载 DC-CIK 细胞治疗胃癌的疗效分析. 中国肿瘤生物治疗杂志, 2016, 23(6): 813-818.
21. 刘小军, 侯小明, 张健, 等. 自体 DC-CIK 细胞联合化疗治疗晚期胃癌的回顾性研究. 中国肿瘤生物治疗杂志, 2016, 23(6): 819-823.
22. 刘清池, 张慧敏, 张玉娜, 等. DC-CIK 细胞清除微小残留白血病的临床研究. 中国肿瘤生物治疗杂志, 2013, 20(4): 398-403.
23. Lee JH, Lee JH, Lim YS, et al. Adjuvant immunotherapy with autologous cytokine-induced killer cells for hepatocellular carcinoma. Gastroenterology, 2015, 148(7): 1383-1391.
24. Liu L, Zhang W, Qi X, et al. Randomized study of autologous cytokine-induced killer cell immunotherapy in metastatic renal carcinoma. Clin Cancer Res, 2012, 18(6): 1751-1759.
25. Pan K, Guan XX, Li YQ, et al. Clinical activity of adjuvant cytokine-induced killer cell immunotherapy in patients with post-mastectomy triple-negative breast cancer. Clin Cancer Res, 2014, 20(11): 3003-3011.
26. Leemhuis T, Wells S, Scheffold C, et al. A phase Ⅰ trial of autologous cytokine-induced killer cells for the treatment of relapsed Hodgkin disease and non-Hodgkin lymphoma. Biol Blood Marrow Transplant, 2005, 11(3): 181-187.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Analysis of clinical efficacy of dendritic cells-cytokine induced killer cells adoptive immunotherapy combined with chemotherapy for patients with gastric cancer after radical gastrectomy

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content