title: Continuous DC-CIK infusions restore CD8+ cellular immunity, physical activity and improve clinical efficacy in advanced cancer patients unresponsive to conventional treatments.
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.
  
  
  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±2.94x10(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.
authors.affiliation: Cancer Center, Beijing Shijitan Hospital, Capital Medical University, Beijing Key Lab of Therapeutic Cancer Vaccines, Beijing, China E-mail : renjun9688@yahoo.com.
authors.forename: Yan-Jie
authors.initials: YJ
authors.lastname: Zhao
authors.forename: Ni
authors.initials: N
authors.lastname: Jiang
authors.forename: Qing-Kun
authors.initials: QK
authors.lastname: Song
authors.forename: Jiang-Ping
authors.initials: JP
authors.lastname: Wu
authors.forename: Yu-Guang
authors.initials: YG
authors.lastname: Song
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Zhang
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Wang
authors.forename: Xin-Na
authors.initials: XN
authors.lastname: Zhou
authors.forename: Hua-Bing
authors.initials: HB
authors.lastname: Yang
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
authors.forename: Herbert Kim
authors.initials: HK
authors.lastname: Lyerly
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003131:Combined Modality Therapy; D055612:Cytokine-Induced Killer Cells / Q000637:transplantation*; D003713:Dendritic Cells / Q000637:transplantation*; D018450:Disease Progression; D015444:Exercise; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D007167:Immunotherapy; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D011379:Prognosis; D011788:Quality of Life