Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Continuous DC-CIK Infusions Restore CD8+ Cellular Immunity, Physical Activity and Improve Clinical Efficacy in Advanced Cancer Patients Unresponsive to Conventional Treatments

  • Zhao, Yan-Jie (Cancer Center, Beijing Shijitan Hospital, Capital Medical University, Beijing Key Lab of Therapeutic Cancer Vaccines) ;
  • Jiang, Ni (Cancer Center, Beijing Shijitan Hospital, Capital Medical University, Beijing Key Lab of Therapeutic Cancer Vaccines) ;
  • Song, Qing-Kun (Cancer Center, Beijing Shijitan Hospital, Capital Medical University, Beijing Key Lab of Therapeutic Cancer Vaccines) ;
  • Wu, Jiang-Ping (Cancer Center, Beijing Shijitan Hospital, Capital Medical University, Beijing Key Lab of Therapeutic Cancer Vaccines) ;
  • Song, Yu-Guang (Cancer Center, Beijing Shijitan Hospital, Capital Medical University, Beijing Key Lab of Therapeutic Cancer Vaccines) ;
  • Zhang, Hong-Mei (Cancer Center, Beijing Shijitan Hospital, Capital Medical University, Beijing Key Lab of Therapeutic Cancer Vaccines) ;
  • Chen, Feng (Cancer Center, Beijing Shijitan Hospital, Capital Medical University, Beijing Key Lab of Therapeutic Cancer Vaccines) ;
  • Zhou, Lei (Cancer Center, Beijing Shijitan Hospital, Capital Medical University, Beijing Key Lab of Therapeutic Cancer Vaccines) ;
  • Wang, Xiao-Li (Cancer Center, Beijing Shijitan Hospital, Capital Medical University, Beijing Key Lab of Therapeutic Cancer Vaccines) ;
  • Zhou, Xin-Na (Cancer Center, Beijing Shijitan Hospital, Capital Medical University, Beijing Key Lab of Therapeutic Cancer Vaccines) ;
  • Yang, Hua-Bing (Cancer Center, Beijing Shijitan Hospital, Capital Medical University, Beijing Key Lab of Therapeutic Cancer Vaccines) ;
  • Ren, Jun (Cancer Center, Beijing Shijitan Hospital, Capital Medical University, Beijing Key Lab of Therapeutic Cancer Vaccines) ;
  • Lyerly, Herbert Kim (Department of Surgery, Duke University Medical Center)
  • Published : 2015.04.03
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Abstract

Background: There are few choices for treatment of advanced cancer patients who do not respond to or tolerate conventional anti-cancer treatments. Therefore this study aimed to deploy the benefits and clinical efficacy of continuous dendritic cell-cytokine induced killer cell infusions in such patients. Materials and Methods: A total of 381 infusions (from 67 advanced cases recruited) were included in this study. All patients underwent peripheral blood mononuclear cell apheresis for the following cellular therapy and dendritic cells-cytokine induced killer cells were expanded in vitro. Peripheral blood T lymphocyte subsets were quantified through flow cytometry to address the cellular immunity status. Clinical efficacy and physical activities were evaluated by RECIST criteria and Eastern Cooperative Oncology Group scores respectively. Logistic regression model was used to estimate the association between cellular infusions and clinical benefits. Results: An average of $5.7{\pm}2.94{\times}10^9$ induced cells were infused each time and patients were exposed to 6 infusions. Cellular immunity was improved in that cytotoxic $CD8^+CD28^+$ T lymphocytes were increased by 74% and suppressive $CD8^+CD28^-$ T lymphocytes were elevated by 16% (p<0.05). Continuous infusion of dendritic cells-cytokine induced killer cells was associated with improvement of both patient status and cellular immunity. A median of six infusions were capable of reducing risk of progression by 70% (95%CI 0.10-0.91). Every elevation of one ECOG score corresponded to a 3.90-fold higher progression risk (p<0.05) and 1% increase of $CD8^+CD28^-$ T cell proportion reflecting a 5% higher risk of progression (p<0.05). Conclusions: In advanced cancer patients, continuous dendritic cell-cytokine induced killer cell infusions are capable of recovering cellular immunity, improving patient status and quality of life in those who are unresponsive to conventional cancer treatment.

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References

  1. Bradley M, Zeytun A, Rafi-Janajreh A, et al (1998). Role of spontaneous and interleukin-2-induced natural killer cell activity in the cytotoxicity and rejection of Fas+ and Fas- tumor cells. Blood, 92, 4248-55.
  2. Chen R, Deng X, Wu H, et al (2014). Combined immunotherapy with dendritic cells and cytokine-induced killer cells for malignant tumors: a systematic review and meta-analysis. Int Immunopharmacol, 22, 451-64. https://doi.org/10.1016/j.intimp.2014.07.019
  3. Choudhury A, Palma M, Mellstedt H (2008). The future of cancer vaccines for non-small-cell lung cancer: ongoing trials. Clin Lung Cancer, 9, 37-44. https://doi.org/10.3816/CLC.2008.s.006
  4. Danielle D, Parker P, Fouladi R, et al (2003). The association between social support, intrusive thoughts, avoidance, and adjustment following an experimental cancer treatment. Psychooncology, 12, 453-62. https://doi.org/10.1002/pon.656
  5. Ferlay J, Soerjomataram I, Ervik M, et al (2013). GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide: IARC CancerBase No. 11 (Internet). Lyon, France: international agency for research on cancer; Available from: http://globocan.iarc.fr, accessed on day/month/year.
  6. Gao D, Li C, Xie X, et al (2014). Autologous tumor lysate-pulsed dendritic cell immunotherapy with cytokine-induced killer cells improves survival in gastric and colorectal cancer patients. PLoS One, 9, 93886. https://doi.org/10.1371/journal.pone.0093886
  7. Han RX, Liu X, Pan P, et al (2014). Effectiveness and safety of chemotherapy combined with dendritic cells co-cultured with cytokine-induced killer cells in the treatment of advanced non-small-cell lung cancer: a systematic review and meta-analysis. PLoS One, 9, 108958. https://doi.org/10.1371/journal.pone.0108958
  8. Heusel J, Wesselschmidt R, Shresta S, et al (1994). Cytotoxic lymphocytes require granzymeB for the rapid induction of DNA fragmentation and apoptosis in allogeneic target cells. Cell, 76, 977-87. https://doi.org/10.1016/0092-8674(94)90376-X
  9. Jin C, Li J, Wang Y, et al (2014). Impact of cellular immune function on prognosis of lung cancer patients after cytokine-induced killer cell therapy. Asian Pac J Cancer Prev, 15, 6009-14. https://doi.org/10.7314/APJCP.2014.15.15.6009
  10. Kagi D, Ledermann B, Burki K, et al (1994). Cytotoxicity mediated by T cells and natural killer cells is greatly impaired inperforin-deficient mice. Nature, 5, 31-7.
  11. Liu P, Chen L, Huang X (2009). The antitumor effects of CIK cells combined with docetaxel against drug-resistant lung adenocarcinoma cell line SPC-A1/DTX in vitro and in vivo. Cancer Biother Radiopharm, 24, 91-8. https://doi.org/10.1089/cbr.2008.0533
  12. Marten A, Ziske C, Schottker B, et al (2001). Interactions between dendritic cells and cytokine-induced killer cells lead to an activation of both populations. J Immunother, 24, 502-10. https://doi.org/10.1097/00002371-200111000-00007
  13. Ren J, Di L, Song G, et al (2013). Selections of appropriate regimen of high-dose chemotherapy combined with adoptive cellular therapy with dendritic and cytokine-induced killer cells improved progression-free and overall survival in patients with metastatic breast cancer: reargument of such contentious therapeutic preferences. Clin Transl Oncol, 15, 780-8. https://doi.org/10.1007/s12094-013-1001-9
  14. Schmidt-Wolf IG, Lefterova P, Johnston V, et al (1996). Sensitivity of multidrug-resistant tumor cell lines to immunologic effector cells. Cell Immunol, 169, 85-90. https://doi.org/10.1006/cimm.1996.0094
  15. Shi L, Zhou Q, Wu J, et al (2012). Efficacy of adjuvant immunotherapy with cytokine-induced killer cells in patients with locally advanced gastric cancer. Cancer Immunol Immunother, 61, 2251-9. https://doi.org/10.1007/s00262-012-1289-2
  16. Shi SB, Tang XY, Tian J, et al (2014). Efficacy of erlotinib plus dendritic cells and cytokine-induced killer cells in maintenance therapy of advanced non-small cell lung cancer. J Immunother, 37, 250-5. https://doi.org/10.1097/CJI.0000000000000015
  17. Song G, Wang X, Jia J, et al (2013). Elevated level of peripheral CD8(+)CD28(-) T lymphocytes are an independent predictor of progression-free survival in patients with metastatic breast cancer during the course of chemotherapy. Cancer Immunol Immunother, 62, 1123-30. https://doi.org/10.1007/s00262-013-1424-8
  18. Wang D, Zhang B, Gao H, et al (2014a). Clinical research of genetically modified dendritic cells in combination with cytokine-induced killer cell treatment in advanced renal cancer. BMC Cancer, 14, 251. https://doi.org/10.1186/1471-2407-14-251
  19. Wang ZX, Cao JX, Liu ZP, et al (2014b). Combination of chemotherapy and immunotherapy for colon cancer in China: a meta-analysis. World J Gastroenterol, 20, 1095-106. https://doi.org/10.3748/wjg.v20.i4.1095
  20. Wang ZX, Cao JX, Wang M, et al (2014c). Adoptive cellular immunotherapy for the treatment of patients with breast cancer: a meta-analysis. Cytotherapy, 16, 934-45. https://doi.org/10.1016/j.jcyt.2014.02.011
  21. Zhao Y, Song Y, Zhang H, et al (2014). Clinical analysis of patients suffering from advanced malignancy with survival time less than 3 months by DC-CIK cells. Cancer Res Prev Treat, 41, 397-400.

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