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Efficacy of postoperative adjuvant transfusion of cytokine-induced killer cells combined with chemotherapy in patients with colorectal cancer

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Abstract

Purpose

To assess the activity and safety of postoperative adjuvant immunotherapy with transfusion of cytokine-induced killer (CIK) cells combined with chemotherapy in patients with colorectal cancer.

Methods

We retrospectively studied 96 consecutive patients with colorectal cancer who were treated with resection between January 2010 and December 2012 as well as adjuvant chemotherapy. Twenty-one of these patients accepted at least 1 cycle of CIK cell transfusion for immunotherapy (CIK group). Disease free survival (DFS), immune cells and treatment related side effects were assessed. The patients were followed up until May 2013.

Results

By the end of follow-up, 10 patients (10.42 %) had died. Eighteen patients (18.75 %) had withdrawn. All the patients in the CIK group are still alive, and only 1 patient had withdrawn. Patients in the CIK group had significantly longer DFS than those in the control group [HR = 0.28, 95 % CI (0.09, 0.91), p = 0.034]. The 2-year DFS rates of patients in the CIK group and the control group were 59.65 ± 24.80 % and 29.35 ± 6.39 %, respectively. The CD4+/CD8+ ratios were significantly lower during the period of chemotherapy than those before chemotherapy (p = 0.0038), while the ratios were significantly higher during the period of CIK cell transfusion than those before CIK therapy (p = 0.0484). There were no immediate adverse reactions to the CIK cell transfusions.

Conclusion

Adjuvant transfusion of CIK cells prolongs DFS in patients with colorectal cancer.

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References

  1. Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics. CA Cancer J Clin 60:277–300

    Article  PubMed  Google Scholar 

  2. Sargent D, Sobrero A, Grothey A, O’Connell MJ, Buyse M, Andre T et al (2009) Evidence for cure by adjuvant therapy in colon cancer: observations based on individual patient data from 20,898 patients on 18 randomized trials. J Clin Oncol 27:872–877

    Article  PubMed  Google Scholar 

  3. Kiessling R, Wasserman K, Horiguchi S, Kono K, Sjoberg J, Pisa P et al (1999) Tumor-induced immune dysfunction. Cancer Immunol Immunother 48:353–362

    Article  PubMed  CAS  Google Scholar 

  4. Ochoa AC, Gromo G, Alter BJ, Sondel PM, Bach FH (1987) Long-term growth of lymphokine-activated killer (LAK) cells: role of anti-CD3, beta-IL 1, interferon-gamma and -beta. J Immunol 138:2728–2733

    PubMed  CAS  Google Scholar 

  5. Yron I, Wood TA Jr, Spiess PJ, Rosenberg SA (1980) In vitro growth of murine T cells. V. The isolation and growth of lymphoid cells infiltrating syngeneic solid tumors. J Immunol 125:238–245

    PubMed  CAS  Google Scholar 

  6. Sangiolo D, Martinuzzi E, Todorovic M, Vitaggio K, Vallario A, Jordaney N et al (2008) Alloreactivity and anti-tumor activity segregate within two distinct subsets of cytokine-induced killer (CIK) cells: implications for their infusion across major HLA barriers. Int Immunol 20:841–848

    Article  PubMed  CAS  Google Scholar 

  7. Pievani A, Borleri G, Pende D, Moretta L, Rambaldi A, Golay J et al (2011) Dual-functional capability of CD3+ CD56+ CIK cells, a T-cell subset that acquires NK function and retains TCR-mediated specific cytotoxicity. Blood 118:3301–3310

    Article  PubMed  CAS  Google Scholar 

  8. Rosenberg SA, Spiess P, Lafreniere R (1986) A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science 233:1318–1321

    Article  PubMed  CAS  Google Scholar 

  9. Linn YC, Lau LC, Hui KM (2002) Generation of cytokine-induced killer cells from leukaemic samples with in vitro cytotoxicity against autologous and allogeneic leukaemic blasts. Br J Haematol 116:78–86

    Article  PubMed  CAS  Google Scholar 

  10. Jiang J, Wu C, Lu B (2013) Cytokine-induced killer cells promote antitumor immunity. J Transl Med 11:83

    Article  PubMed  CAS  Google Scholar 

  11. Kim HM, Lim J, Yoon YD, Ahn JM, Kang JS, Lee K et al (2007) Anti-tumor activity of ex vivo expanded cytokine-induced killer cells against human hepatocellular carcinoma. Int Immunopharmacol 7:1793–1801

    Article  PubMed  CAS  Google Scholar 

  12. Sun S, Li XM, Li XD, Yang WS (2005) Studies on inducing apoptosis effects and mechanism of CIK cells for MGC-803 gastric cancer cell lines. Cancer Biother Radiopharm 20:173–180

    Article  PubMed  CAS  Google Scholar 

  13. Kim HM, Lim J, Park SK, Kang JS, Lee K, Lee CW et al (2007) Antitumor activity of cytokine-induced killer cells against human lung cancer. Int Immunopharmacol 7:1802–1807

    Article  PubMed  CAS  Google Scholar 

  14. Finke S, Trojaneck B, Lefterova P, Csipai M, Wagner E, Kircheis R et al (1998) Increase of proliferation rate and enhancement of antitumor cytotoxicity of expanded human CD3+ CD56+ immunologic effector cells by receptor-mediated transfection with the interleukin-7 gene. Gene Ther 5:31–39

    Article  PubMed  CAS  Google Scholar 

  15. Wang XP, Xu M, Gao HF, Zhao JF, Xu KC (2013) Intraperitoneal perfusion of cytokine-induced killer cells with local hyperthermia for advanced hepatocellular carcinoma. World J Gastroenterol 19:2956–2962

    PubMed  CAS  Google Scholar 

  16. Schmidt-Wolf IG, Negrin RS, Kiem HP, Blume KG, Weissman IL (1991) Use of a SCID mouse/human lymphoma model to evaluate cytokine-induced killer cells with potent antitumor cell activity. J Exp Med 174:139–149

    Article  PubMed  CAS  Google Scholar 

  17. Schmidt-Wolf IG, Finke S, Trojaneck B, Denkena A, Lefterova P, Schwella N et al (1999) Phase I clinical study applying autologous immunological effector cells transfected with the interleukin-2 gene in patients with metastatic renal cancer, colorectal cancer and lymphoma. Br J Cancer 81:1009–1016

    Article  PubMed  CAS  Google Scholar 

  18. Jiang J, Xu N, Wu C, Deng H, Lu M, Li M et al (2006) Treatment of advanced gastric cancer by chemotherapy combined with autologous cytokine-induced killer cells. Anticancer Res 26:2237–2242

    PubMed  CAS  Google Scholar 

  19. Wu C, Jiang J, Shi L, Xu N (2008) Prospective study of chemotherapy in combination with cytokine-induced killer cells in patients suffering from advanced non-small cell lung cancer. Anticancer Res 28:3997–4002

    PubMed  CAS  Google Scholar 

  20. Su X, Zhang L, Jin L, Ye J, Guan Z, Chen R et al (2010) Immunotherapy with cytokine-induced killer cells in metastatic renal cell carcinoma. Cancer Biother Radiopharm 25:465–470

    Article  PubMed  CAS  Google Scholar 

  21. Liu L, Zhang W, Qi X, Li H, Yu J, Wei S et al (2012) Randomized study of autologous cytokine-induced killer cell immunotherapy in metastatic renal carcinoma. Clin Cancer Res 18:1751–1759

    Article  PubMed  CAS  Google Scholar 

  22. Dougan M, Dranoff G (2009) Immune therapy for cancer. Annu Rev Immunol 27:83–117

    Article  PubMed  CAS  Google Scholar 

  23. Hui D, Qiang L, Jian W, Ti Z, Da-Lu K (2009) A randomized, controlled trial of postoperative adjuvant cytokine-induced killer cells immunotherapy after radical resection of hepatocellular carcinoma. Dig Liver Dis 41:36–41

    Article  PubMed  Google Scholar 

  24. Shi L, Zhou Q, Wu J, Ji M, Li G, Jiang J et al (2012) Efficacy of adjuvant immunotherapy with cytokine-induced killer cells in patients with locally advanced gastric cancer. Cancer Immunol Immunother 61:2251–2259

    Article  PubMed  CAS  Google Scholar 

  25. Edinger M, Cao YA, Verneris MR, Bachmann MH, Contag CH, Negrin RS (2003) Revealing lymphoma growth and the efficacy of immune cell therapies using in vivo bioluminescence imaging. Blood 101:640–648

    Article  PubMed  CAS  Google Scholar 

  26. Robinson E, Segal R, Struminger L, Faraggi D, El’ad-Yarum R, Mekori T (1999) Lymphocyte subpopulations in patients with multiple primary tumors. Cancer 85:2073–2076

    PubMed  CAS  Google Scholar 

  27. Milasiene V, Stratilatovas E, Norkiene V (2007) The importance of T-lymphocyte subsets on overall survival of colorectal and gastric cancer patients. Medicina (Kaunas) 43:548–554

    Google Scholar 

  28. Cho MY, Joh YG, Kim NR, Jung SI, Bae JW, Kim YC et al (2002) T-lymphocyte subsets in patients with AJCC stage III gastric cancer during postoperative adjuvant chemotherapy. American Joint Committee on Cancer. Scand J Surg 91:172–177

    PubMed  CAS  Google Scholar 

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Oncology, Guangdong Provincial Hospital of Chinese Medicine, N.O. 111, Dade Road, Guangzhou, 510120, Guangdong Province, China

    Yanjuan Zhu, Haibo Zhang, Yong Li, Jianping Bai, Lirong Liu, Yihong Liu, Yanchun Qu & Xin Qu

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  1. Yanjuan Zhu
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  2. Haibo Zhang
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  3. Yong Li
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  4. Jianping Bai
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  5. Lirong Liu
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  6. Yihong Liu
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  7. Yanchun Qu
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  8. Xin Qu
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Correspondence to Haibo Zhang.

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Zhu, Y., Zhang, H., Li, Y. et al. Efficacy of postoperative adjuvant transfusion of cytokine-induced killer cells combined with chemotherapy in patients with colorectal cancer. Cancer Immunol Immunother 62, 1629–1635 (2013). https://doi.org/10.1007/s00262-013-1465-z

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  • DOI: https://doi.org/10.1007/s00262-013-1465-z

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