Cytokine-induced killer cell/dendritic cell combined with cytokine-induced killer cell immunotherapy for treating advanced gastrointestinal cancer

Hansong Du, Jia Yang, Ying Zhang, Hansong Du, Jia Yang, Ying Zhang

Abstract

Background: This study aimed to investigate the efficacy and safety of cytokine-induced killer (CIK)/dendritic cell combined with CIK (DC-CIK) cell therapy in advanced gastrointestinal cancer (GIC).

Methods: The PubMed, Cochrane library, and Embase were searched to conduct a meta-analysis of clinical controlled trials to evaluate the efficacy and safety of CIK/DC-CIK cell therapy in advanced GIC. The pooled risk ratios (RRs) or weighted mean difference (WMD) with 95% confidence intervals (95% CIs) were calculated.

Results: A total of nine studies with 1113 patients were identified. The overall survival (RR = 1.84, 95% CI = 1.41-2.40, Pheterogeneity = 0.654, I2 = 0%), progression-free survival (RR = 1.99, 95% CI = 1.52-2.60, Pheterogeneity = 0.727, I2 = 0%), and quality of life (WMD = 16.09, 95% CI = 1.66-30.52, Pheterogeneity < 0.001, I2 = 98.8%) were significantly improved in patients who received chemotherapy combined with CIK/DC-CIK cells, and no severe adverse events were reported.

Conclusion: This meta-analysis suggested that the combination of CIK/DC-CIK immunotherapy and chemotherapy was safe and applicable for patients with advanced GIC. It is a feasible choice to prolong survival and improve quality of life.

Keywords: Advanced gastrointestinal cancer; Cytokine-induced killer; Dendritic cell; Meta-analysis; Systematic review.

Conflict of interest statement

All authors declare that they have no any conflict of interests.

Figures

Fig. 1
Fig. 1
Flow diagram of study identification
Fig. 2
Fig. 2
Risk-of-bias assessments for the randomized trials included in the meta-analysis. a Risk-of-bias summary. b Risk-of-bias graph. Symbols: (+), Low risk of bias; (?), unclear risk of bias; and (−), high risk of bias
Fig. 3
Fig. 3
Forest plot of the comparison of survival. a Overall survival (OS). b Progression-free survival
Fig. 4
Fig. 4
Forest plot of the comparison of complete response (CR), partial response (PR), and overall response rate (ORR)
Fig. 5
Fig. 5
Sensitivity analysis examining the influence of individual study on pooled results. a Overall survival. b Progression-free survival. c Partial response. d Overall response rate
Fig. 6
Fig. 6
Funnel plot for publication bias. Each point represents a separate study for the indicated association. a Funnel plot of OS. b Trim-and-fill plot of OS

References

    1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.
    1. Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2014 (ver. 4). Gastric Cancer. 2017;20(1):1–19. PMID: PMC5215069.
    1. Suzuki H, Gotoda T, Sasako M, Saito D. Detection of early gastric cancer: misunderstanding the role of mass screening. Gastric Cancer. 2006;9(4):315–319.
    1. McFarland EG, Levin B, Lieberman DA, Pickhardt PJ, Johnson CD, Glick SN, et al. Revised colorectal screening guidelines: joint effort of the American Cancer Society, U.S. multisociety task force on colorectal Cancer, and American College of Radiology. Radiology. 2008;248(3):717–720.
    1. Dehghanzadeh R, Jadidi-Niaragh F, Gharibi T, Yousefi M. MicroRNA-induced drug resistance in gastric cancer. Biomed Pharmacother. 2015;74:191–199.
    1. Zugazagoitia J, Guedes C, Ponce S, Ferrer I, Molina-Pinelo S, Paz-Ares L. Current challenges in Cancer treatment. Clin Ther. 2016;38(7):1551–1566.
    1. Lee JH, Lee JH, Lim YS, Yeon JE, Song TJ, Yu SJ, et al. Adjuvant immunotherapy with autologous cytokine-induced killer cells for hepatocellular carcinoma. Gastroenterology. 2015;148(7):1383–1391.
    1. Nakagawa S, Matsuoka Y, Ichihara H, Yoshida H, Yoshida K, Ueoka R. New cancer immunotherapy using autologous lymphocytes activated with trastuzumab. Biol Pharm Bull. 2012;35(8):1213–1215.
    1. Palucka K, Banchereau J. Cancer immunotherapy via dendritic cells. Nat Rev Cancer. 2012;12(4):265–277.
    1. Jiang J, Wu C, Lu B. Cytokine-induced killer cells promote antitumor immunity. J Transl Med. 2013;11:83.
    1. Yang T, Zhang W, Wang L, Xiao C, Wang L, Gong Y, et al. Co-culture of dendritic cells and cytokine-induced killer cells effectively suppresses liver cancer stem cell growth by inhibiting pathways in the immune system. BMC Cancer. 2018;18(1):984.
    1. Jiang J, Xu N, Wu C, Deng H, Lu M, Li M, et al. Treatment of advanced gastric cancer by chemotherapy combined with autologous cytokine-induced killer cells. Anticancer Res. 2006;26(3b):2237–2242.
    1. Shi L, Zhou Q, Wu J, Ji M, Li G, Jiang J, et al. Efficacy of adjuvant immunotherapy with cytokine-induced killer cells in patients with locally advanced gastric cancer. Cancer Immunol Immunother. 2012;61(12):2251–2259.
    1. Zhao H, Fan Y, Li H, Yu J, Liu L, Cao S, et al. Immunotherapy with cytokine-induced killer cells as an adjuvant treatment for advanced gastric carcinoma: a retrospective study of 165 patients. Cancer Biother Radiopharm. 2013;28(4):303–309.
    1. Lin T, Song C, Chuo DY, Zhang H, Zhao J. Clinical effects of autologous dendritic cells combined with cytokine-induced killer cells followed by chemotherapy in treating patients with advanced colorectal cancer: a prospective study. Tumour Biol. 2016;37(4):4367–4372.
    1. Mu Y, Wang WH, Xie JP, Zhang YX, Yang YP, Zhou CH. Efficacy and safety of cord blood-derived dendritic cells plus cytokine-induced killer cells combined with chemotherapy in the treatment of patients with advanced gastric cancer: a randomized phase II study. Onco Targets Ther. 2016;9:4617–4627.
    1. Zhao H, Wang Y, Yu J, Wei F, Cao S, Zhang X, et al. Autologous cytokine-induced killer cells improves overall survival of metastatic colorectal Cancer patients: results from a phase II clinical trial. Clin Colorectal Cancer. 2016;15(3):228–235.
    1. Peng H, Yao M, Fan H, Song L, Sun J, Zhou Z, et al. Effects of autologous cytokine-induced killer cells infusion in colorectal Cancer patients: a prospective study. Cancer Biother Radiopharm. 2017;32(6):221–226.
    1. Wang Y, Wang C, Xiao H, Niu C, Wu H, Jin H, et al. Adjuvant treatment combining cellular immunotherapy with chemotherapy improves the clinical outcome of patients with stage II/III gastric cancer. Cancer Med. 2017;6(1):45–53.
    1. Xie Y, Huang L, Chen L, Lin X, Chen L, Zheng Q. Effect of dendritic cell-cytokine-induced killer cells in patients with advanced colorectal cancer combined with first-line treatment. World J Surg Oncol. 2017;15(1):209.
    1. Duval S, Tweedie R. Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics. 2000;56(2):455–463.
    1. Yan Z, Xiong Y, Xu W, Gao J, Cheng Y, Wang Z, et al. Identification of hsa-miR-335 as a prognostic signature in gastric cancer. PLoS One. 2012;7(7):e40037.
    1. Schmidt-Wolf IG, Negrin RS, Kiem HP, Blume KG, Weissman IL. Use of a SCID mouse/human lymphoma model to evaluate cytokine-induced killer cells with potent antitumor cell activity. J Exp Med. 1991;174(1):139–149.
    1. Scheffold C, Brandt K, Johnston V, Lefterova P, Degen B, Schontube M, et al. Potential of autologous immunologic effector cells for bone marrow purging in patients with chronic myeloid leukemia. Bone Marrow Transplant. 1995;15(1):33–39.
    1. Schmidt-Wolf IG, Lefterova P, Johnston V, Scheffold C, Csipai M, Mehta BA, et al. Sensitivity of multidrug-resistant tumor cell lines to immunologic effector cells. Cell Immunol. 1996;169(1):85–90.
    1. Ren X, Yu J, Liu H, Zhang P, An X, Zhang N, et al. Th1 bias in PBMC induced by multicycles of auto-CIKs infusion in malignant solid tumor patients. Cancer Biother Radiopharm. 2006;21(1):22–33.
    1. Lu PH, Negrin RS. A novel population of expanded human CD3+CD56+ cells derived from T cells with potent in vivo antitumor activity in mice with severe combined immunodeficiency. J Immunol. 1994;153(4):1687–1696.
    1. Ishigami S, Natsugoe S, Tokuda K, Nakajo A, Che X, Iwashige H, et al. Prognostic value of intratumoral natural killer cells in gastric carcinoma. Cancer. 2000;88(3):577–583.
    1. Wang FS, Liu MX, Zhang B, Shi M, Lei ZY, Sun WB, et al. Antitumor activities of human autologous cytokine-induced killer (CIK) cells against hepatocellular carcinoma cells in vitro and in vivo. World J Gastroenterol. 2002;8(3):464–468.
    1. Kim HM, Lim J, Park SK, Kang JS, Lee K, Lee CW, et al. Antitumor activity of cytokine-induced killer cells against human lung cancer. Int Immunopharmacol. 2007;7(13):1802–1807.
    1. Wang P, Yu JP, Gao SY, An XM, Ren XB, Wang XG, et al. Experimental study on the treatment of intracerebral glioma xenograft with human cytokine-induced killer cells. Cell Immunol. 2008;253(1–2):59–65.
    1. Sun S, Li XM, Li XD, Yang WS. Studies on inducing apoptosis effects and mechanism of CIK cells for MGC-803 gastric cancer cell lines. Cancer Biother Radiopharm. 2005;20(2):173–180.
    1. Wang X, Tang S, Cui X, Yang J, Geng C, Chen C, et al. Cytokine-induced killer cell/dendritic cell-cytokine-induced killer cell immunotherapy for the postoperative treatment of gastric cancer: a systematic review and meta-analysis. Medicine (Baltimore) 2018;97(36):e12230.
    1. Zhao M, Li H, Li L, Zhang Y. Effects of a gemcitabine plus platinum regimen combined with a dendritic cell-cytokine induced killer immunotherapy on recurrence and survival rate of non-small cell lung cancer patients. Exp Ther Med. 2014;7(5):1403–1407.
    1. Ma Y, Xu YC, Tang L, Zhang Z, Wang J, Wang HX. Cytokine-induced killer (CIK) cell therapy for patients with hepatocellular carcinoma: efficacy and safety. Exp Hematol Oncol. 2012;1(1):11.
    1. Wang D, Zhang B, Gao H, Ding G, Wu Q, Zhang J, et al. Clinical research of genetically modified dendritic cells in combination with cytokine-induced killer cell treatment in advanced renal cancer. BMC Cancer. 2014;14:251.
    1. Li JJ, Gu MF, Pan K, Liu LZ, Zhang H, Shen WX, et al. Autologous cytokine-induced killer cell transfusion in combination with gemcitabine plus cisplatin regimen chemotherapy for metastatic nasopharyngeal carcinoma. J Immunother. 2012;35(2):189–195.
    1. Schmeel LC, Schmeel FC, Coch C, Schmidt-Wolf IG. Cytokine-induced killer (CIK) cells in cancer immunotherapy: report of the international registry on CIK cells (IRCC) J Cancer Res Clin Oncol. 2015;141(5):839–849.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir