|Year : 2019 | Volume
| Issue : 4 | Page : 72-76
Progress in clinical follow-up study of dendritic cells combined with cytokine-induced killer for stomach cancer
Ling Wang, Run Wan, Cong Chen, Ruiliang Su, Yumin Li
Lanzhou University Second Hospital; Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou University Second Hospital, Lanzhou, Gansu, People's Republic of China
|Date of Submission||02-Nov-2019|
|Date of Acceptance||06-Dec-2019|
|Date of Web Publication||26-Dec-2019|
Dr. Yumin Li
Lanzhou University Second Hospital, No. 81 of Cuiyingmen, Linxia Road, Chengguan District, Lanzhou 730000
People's Republic of China
Source of Support: None, Conflict of Interest: None
Stomach cancer is a common malignant disease and is generally associated with mortality. Immunotherapy, including dendritic cells combined with cytokine-induced killer cells (DC-CIK), poses a significant presence. Follow-up plays a vital role in immunotherapy with stomach cancer by effectively predicting recurrence, promptly diagnosing disease, and early intervening to improve clinical outcome and survival rate. Follow-up guideline takes into these terms which are response evaluation criteria in solid tumors, health-related quality of life, tumor markers, T-lymphocyte subsets, and cytokine on the basis of the National Comprehensive Cancer Network guideline. At the same time, the high-level follow-up team is necessary. Hitherto, there is no specific follow-up guide for immunotherapy. This article reviews the follow-up of DC-CIK with stomach cancer, and it is expected that more researchers focus on this issue to draw up utility guidelines of immunotherapy for stomach cancer.
Keywords: Dendritic cells combined with cytokine-induced killer, follow-up, immunotherapy, stomach cancer
|How to cite this article:|
Wang L, Wan R, Chen C, Su R, Li Y. Progress in clinical follow-up study of dendritic cells combined with cytokine-induced killer for stomach cancer. Cancer Transl Med 2019;5:72-6
|How to cite this URL:|
Wang L, Wan R, Chen C, Su R, Li Y. Progress in clinical follow-up study of dendritic cells combined with cytokine-induced killer for stomach cancer. Cancer Transl Med [serial online] 2019 [cited 2020 May 28];5:72-6. Available from: http://www.cancertm.com/text.asp?2019/5/4/72/274031
| Introduction|| |
Stomach cancer ranks fifth for the number of new global cancer cases, approximately 1.0 million diagnoses are estimated in 2018, contributing about 5.7% of the total cancer incidence burden. Stomach cancer is the third type in terms of the number of deaths, 783,000 deaths occurred, accounting for 8.2% of the cancer deaths. Although signs of progress in surgical techniques, chemotherapeutic regimens, radiations and targeted therapies, clinical outcomes of patients with stomach cancer remain poor. Abundant patients suffer severe side effects and recurrence, even more, the 5-year survival rate is under 5% in advanced unresectable or metastatic disease and of which approximately 80% of patients were diagnosed. Hitherto, biological immunotherapy makes a breakthrough in the aspect of anticancer. As a novel type of immunotherapies, dendritic cells (DCs) combined with cytokine-induced killer cells (CIKs) generate remarkable killing effects on tumor cells., DCs are professional antigen-presenting cells, which present tumor antigens to T-lymphocytes and induce antitumor immune responses. DCs function as stimulators of effective T-cells through the promotion of the generation of helper and cytotoxic T-cells.,, Since CIK traits as recognizing cancer cells, against tumor activity of T-lymphocytes and the non-MHC-restricted tumor-killing ability of natural killer cells, it performs far better in proliferation rate, antitumor activity, and antitumor spectrum.,,, DC-CIK stimulates the immune response of the body to fight tumor cells by the retransformation effect of the cells which depends on the high killing activity of effector cells and the autologous immune system. The virtue of DC-CIK treatment is that the high proliferation rate and cytotoxic activity against adequate cancer types, the simple and mild culture conditions, little adverse reactions, and satisfactory patient compliance.,, DC-CIK has been widely used to treat stomach cancer as a clinical trial (Flowchart for the treatment of DC-CIK is in [Figure 1]) that brings forth enhanced immune function, improved survival, and better clinical responses for patients with stomach cancer.
|Figure 1: Flowchart for the treatment of dendritic cells combined with cytokine-induced killer|
Click here to view
Follow-up plays a crucial role in clinical trials. The guidelines of the National Comprehensive Cancer Network (NCCN) for stomach cancer cover the follow-up items. This review summarizes follow-up clinical results obtained so far with DC-CIK treatment for stomach cancer and discusses the novel strategies to improve the quality of clinical trials.
| Immune Response Evaluation Criteria in Solid Tumours|| |
Changes in tumor burden play a critical role in evaluating cancer therapeutic. The response evaluation criteria in solid tumors (RECIST), which are conventional radiological response criteria, have been used in clinical trials of DC-CIK for stomach cancer.,,, As there are differences in response mechanisms of tumors treatment between immunotherapies and chemotherapeutic agents or targeted therapies, precision estimation of the response is a big tissue. For example, pseudoprogression (PsPD) could induce in misinterpretation of the patient's status and generate suboptimal clinical decisions. Then, PsPD is immune-related response patterns, such as an initial increase in tumor burden or the appearance of new lesions. Whether new lesion or tumor burden was measured, and how many were captured. Taking this into account, the RECIST working group published a proposition of new criteria called iRECIS (immune) that is a standard approach, which is appropriate for solid tumor measurements and objective change of tumor size in immunotherapy trials. In addition, it defines the minimum data points required from future trials and those currently in development to facilitate the compilation of a data library to use to later validate immune RECIST (iRECIST). In conclusion, iRECIST should be recommended in clinical trials thereafter.
| Health-Related Quality of Life|| |
Health-related quality of life (HRQOL) is vital for health-care professionals, involving in the oncology setting. The United States Food and Drug Administration recognizes the benefits of HRQOL as a basis for approval of new anticancer drugs, and HRQOL was included as the primary endpoint of many international research groups. The four components of physical, psychological/emotional, social, and occupational well-being make up HRQOL, which is a subjective concept., Currently, a lot of questionnaires are used to measure HRQOL among oncological patients. Existing DC-CIK clinical trial refers to KPS,,,,,, which has own limitations while assessing patient prognosis at the end of life. For instance, limited physical functioning was focalized among cancer patients. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) and the Functional Assessment of Cancer Therapy-General (FACT-G) have a wide range of applications in QOL assessment questionnaires for cancer patients. Quality of Life Questionnaire-QLQ-STO22 and FACT-Gastric (FACT-Ga) are stomach cancer-specific questionnaires. The QLQ-STO22 consists of 52 items instrument, emphasizing the functional and physical concerns of patients, whereas the FACT-Ga comprises 47 items, underlining social and emotional issues to some extent. HQL may be used to monitor morbidity and mortality and provide treatment decisions. On the basis of the specific patient characteristics and objects of the study, the optimal questionnaire should be established. Hypothetically, we may firmly arrive at an indisputable specific questionnaire for stomach cancer which can provide essential information regarding patients' QOL and the efficacy of immunotherapy, including DC-CIK.
| Tumor Markers|| |
Carbohydrate antigen (CA) 724, cancer antigen embryonic antigen (CEA), CA199, alpha-fetoprotein (AFP), and CA125 are widely detected in clinical practice of stomach cancer., CA724 is the most effective marker for detecting advanced stomach cancer and has the highest positive rate in nodal involvement or serosal invasion patients among these tumor markers. CEA is strongly correlated with the tumor, node, and metastases stage. The CEA is connected with tumor size, vascular involvement, serosal invasion, lymph node, and hepatic metastases in cancer patients. CA199 was frequently reported to be connected with nodal involvement among various clinicopathological factors, such as tumor depth, nodal involvement, peritoneal metastases, and stages. The combinations of CEA, CA199, and CA724 are the most effective ways before surgery or chemotherapy, which may be available to detect recurrence or evaluation of the response. AFP is of value with detecting and predicting liver metastases. CA125 is serviceable for monitoring peritoneal metastases. Nevertheless, minority clinical trials have not detected some of the above-mentioned serum tumor markers.,,,, Although the five serum markers are insensitive for screening early stomach cancer, they are useful in monitoring after treatment for stomach cancer such as detecting recurrence and distant metastasis and predicting survival. The guideline, which is the clinical utility of serum markers for stomach cancer patients during treatment, should be established through a phase III prospective randomized trial for DC-CIK.
| T-Lymphocyte Subsets and Cytokine|| |
The immune function and T-lymphocyte subsets percentage in the peripheral blood of cancer patients is distinctive from noncancer patients. CD3+ cells reflect the overall cell immune state of organisms and are the sum of the number of CD4+ and CD8+ cells. CD4+ T-cells, namely helper T-cells, including in Th1-cells and Th2-cells, which effect by recruiting CD8+ T-cells and activating macrophages. Th1 cells build up cytotoxicity of killer cells and induce delayed-type hypersensitivity, whereas Th2-cells lead to the immunity escape of tumor cells. The counterbalance between Th1- and Th2-cells matters in immunotherapy. It is observed that the absolute number and percentage of CD3+ and CD3+ CD4+ T-cells in peripheral blood of the normal healthy controls were obviously high than the advanced stomach cancer patients., CD3+CD8+ cytotoxic T-lymphocytes (CTLs) take effect in immune defense. CD3+CD4+ T-cells act a part in anti-tumor immune responses through promoting the proliferation of CD3+CD8 + CTLs. Interaction between CD4+ and CD8+ T-cells affects cytotoxicity against tumors., Survival rates of stage III stomach cancer patients are positively correlated with percentages of CD4+ lymphocytes and the absolute number of CD8+ cells, controversially, lower percentages of CD8+ lymphocytes are associated with longer survival in another article., Regulatory T-cells (Tregs), defined as CD3+CD4+CD25+/CD4+CD25+Foxp3+ T-cells, work by repressing CD3+CD8+ T-cell action and is relevant to poor prognosis in cancers., CIK refers to two main heterogeneous cell subsets, CD3+/CD56 + and CD3+/CD58+. CIK could direct contact and secrete cytokines, such as interleukin-2 (IL-2), interferon-γ (IFN-γ), and tumor necrosis factor (TNF), and then induce apoptosis and inhibit the proliferation of tumor cells., When co-cultured with CIK and DC, the expression of cytokines such as IL-2, IFN-r, TNF, IL-12, and the rates of the main effector cells were increased, which strengthen the cytotoxicity of CIK. Almost all clinical trials of DC-CIK have measured T-lymphocyte subsets and cytokine levels to assess immune status.,,,,,,,,, It is reported that indicators of reactive immune status, for instance, the percentage of lymphocyte subsets (CD3+, CD4 + and CD3 − CD56+, CD3 + CD56+), the levels of IL-12 and IFN-γ, were apparently enhanced by the CIK/DC-CIK therapy. There is no doubt that we may firmly arrive at an indisputable guideline about T-lymphocyte subsets and cytokine and implemented in clinical studies for DC-CIK.
| Discussion|| |
The therapeutic mechanism of stomach cancer has changed when immunotherapy such as PD-1 and CAR-T have been applied in clinical treatment, new examining item, involving in positron emission tomography–computed tomography (CT) and CT colonography, have been a prognostic factor in the clinical treatment of breast cancer. The current guidelines of follow-up are deficient. To ensure consistent design and data collection and ultimate validation of the guideline, the new specific guideline of stomach cancer for immunotherapy (DC-CIK) should be established where optimize items mentioned in this article and based on NCCN guidelines for stomach cancer. To performance bias of follow-up, excellent follow-up team and professional management are irreplaceable. First, the follow-up team consists of doctors, nurses, epidemiologists, statistics, psychologists, and nutritionists. All members of the follow-up team are informed that humanistic care matters and they should not withdraw optionally. The members should be rigorously trained in related-study knowledge and communication skills. Nurses take charge of keeping in contact with doctors and patients, fixing the time, filling out and collecting booklets, addressing the problems, and reflecting on the manager. Even if patients change hospitals, the follow-up should be insisted on by contacting the staff of the hospital. Epidemiologists and statisticians are in charge of statistical data and deal with problems in the study. NCCN guideline refers to vitamin and Iron; nutritionists give dietary instruction for participants. Cancer is a risk factor for developing emotional disturbances, especially depression and risk of suicide among cancer patients compared with the general population., Psychologists are responsible for psychological therapy. The leader of the follow-up is made arrangements and responsible for coordinating with all things. Second, the pattern of follow-up needs to integrate outpatient, telephone, network, and home follow-up. By home follow-up, investigating the needs of individuals and families to solve the difficulties during the treatment. Explaining disease knowledge and answering questions by network follow-up. In addition, the outpatient follow-up should give first to place. Doctors in charge who are more trusted by patients and communication are more effective are responsible for carrying out content and filling out the booklet in the outpatient department. Third, standardized management is also important. IT is needed that setting up electronic archives, draft booklet which is owned by doctors and patients, respectively. Taking booklets with patients, they can immediately fill in information such as side effects, as well as stimulate a sense of participation to reduce the expulsion rate.
In sum, it is irreplaceable to design and implement a follow-up system for improving the validity and safety of immunotherapy (DC-CIK) with stomach cancer patients.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. 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.
Piazuelo MB, Correa P. Gastric cancer: overview. Colomb Med (Cali)
2013; 44(3): 192–201.
Zhu XP, Xu YH, Zhou J, Pan XF. A clinical study evaluating dendritic and cytokine-induced killer cells combined with concurrent radiochemotherapy for stage IIIB non-small cell lungcancer. Genet Mol Res
2015; 14(3): 10228–35.
Mao Q, Li L, Zhang C, Sun Y, Liu S, Cui S. Clinical effects of immunotherapy of DC-CIK combined with chemotherapy in treating patients with metastatic breast cancer. Pak J Pharm Sci
2015; 28(Suppl 3): 1055–8.
Steinman RM, Nussenzweig MC. Dendritic cells: features and functions. Immunol Rev
1980; 53: 127–47.
Wei XC, Yang DD, Han XR, Zhao YA, Li YC, Zhang LJ, Wang JJ. Bioactivity of umbilical cord blood dendritic cells and anti-leukemia effect. Int J Clin Exp Med
2015; 8(10): 19725–30.
Wei XC, Zhai XH, Han XR, Yang DD, Wang QS. Influence of dendritic cells on biological activity of the homologous CIK cells and its anti-leukemia effect in vitro
. Zhongguo Shi Yan Xue Ye Xue Za Zhi
2010; 18(4): 946–51.
Qu HQ, Zhou XS, Zhou XL, Wang J. Effect of DC-CIK cell on the proliferation, apoptosis and differentiation of leukemia cells. Asian Pac J Trop Med
2014; 7(8): 659–62.
Shan CC, Shi LR, Ding MQ, Zhu YB, Li XD, Xu B, Jiang JT, Wu CP. Cytokine-induced killer cells co-cultured with dendritic cells loaded with the protein lysate produced by radiofrequency ablation induce a specific antitumor response. Oncol Lett
2015; 9(4): 1549–56.
Zhang Z, Wang L, Luo Z, Zhao X, Huang J, Li H, Yang S, Zhao X, Zhang L, Li L, Wang F, Huang L, Zhang Y. Efficacy and safety of cord blood-derived cytokine-induced killer cells in treatment of patients with malignancies. Cytotherapy
2015; 17(8): 1130–8.
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): 4367–72.
Zhong R, Han B, Zhong H. A prospective study of the efficacy of a combination of autologous dendritic cells, cytokine-induced killer cells, and chemotherapy in advanced non-small cell lung cancer patients. Tumour Biol
2014; 35(2): 987–94.
Jin CG, Chen XQ, Li J, Wu ZP, Liu X, Wang XC. Moderating effects and maintenance of lung cancer cellular immune functions by CIK cell therapy. Asian Pac J Cancer Prev
2013; 14(6): 3587–92.
Shi SB, Ma TH, Li CH, Tang XY. Effect of maintenance therapy with dendritic cells: cytokine-induced killer cells in patients with advanced non-small cell lung cancer. Tumori
2012; 98(3): 314–9.
Mu Y, Zhou CH, Chen SF, Ding J, Zhang YX, Yang YP, Wang WH. Effectiveness and safety of chemotherapy combined with cytokine-induced killer cell/dendritic cell-cytokine-induced killer cell therapy for treatment of gastric cancer in China: a systematic review and meta-analysis. Cytotherapy
2016; 18(9): 1162–77.
Available from: https://www.nccn.org/professionals/physician_gls/default.aspx. [Last accessed on 2019 Sep 08].
Kim C, Prasad V. Cancer drugs approved on the basis of a surrogate end point and subsequent overall survival: an analysis of 5 years of US Food and Drug Administration Approvals. JAMA Intern Med
2015; 175(12): 1992–4.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer
2009; 45(2): 228–47.
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(12): 4617–27.
Jin J, Dou JX, Liu ZY, Liang PF, Qiao LK, Sun WW. Efficacy of cytokine-induced killer cells co-cultured with dendritic cells targeting gastric cancer stem cells in patients with advanced gastric cancer. Chin J Prev Control Chronic Dis
2015; 12: 938–9.
Chen Q, Dou JX, Zhang L. Clinical study on influence of Kanglaite injection combined DC-CIK cells on immune index among patients with malignant tumor. Occup Health
2016; 13: 1870–2.
Ding Y, Chen YQ, Li QZ, Mi YJ, Yan JH, Ye YH. Influence of Helicobacter pylori
infection on autologous DC-CIK maintenance therapy in the advanced gastric cancer patients. Chin J Cancer Biother
Chiou VL, Burotto M. Pseudoprogression and immune-related response in solid tumors. J Clin Oncol
2015; 3 (31): 3541–3.
Wolchok JD, Hoos A, O'Day S, Weber JS, Hamid O, Lebbe C, Maio M, Binder M, Bohnsack O, Nichol G, Humphrey R, Hodi FS. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res
2009; 15(23): 7412–20.
Seymour L, Bogaerts J, Perrone A, Ford R, Schwartz LH, Mandrekar S, Lin NU, Litiere S, Dancey J, Chen A, Hodi FS, Therasse P, Hoekstra OS, Shankar LK, Wolchok JD, Ballinger M, Caramella C, de Vries EG, group Rw. iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol
2017; 18(3): e143–52.
Sanders C, Egger M, Donovan J, Tallon D, Frankel S. Reporting on quality of life in randomised controlled trials: bibliographic study. BMJ
1998; 317(7167): 1191–4.
Bottomley A. The cancer patient and quality of life. The Oncol
2002; 7(2): 120–5.
Fallowfield L. Quality of life: a new perspective for cancer patients. Nat Rev Cancer
2002; 2(11): 873–9.
Cui Y, Bai B, Wen Y, Kuang S. Clinical study of autologous cytokine-induced killer cells combined with XELOX regimen in the treatment of senile advanced gastric cancer. Zhonghua Wei Chang Wai Ke Za Zhi
2014; 17(7): 698–701.
Wang JS, Xie ZX, Li HJ. Short-term efficacy of DC-CIK biotherapy combined with chemotherapy for patients with advanced gastric cancer. J Pract Oncol
2016; 1(11): 38–42.
Shan HH, Huang GQ. Clinical efficacy of DC-CIK combined with chemotherapy in the treatment of 45 cases patients with advanced gastric cancer. Chin J Gastroenterol Hepatol
Fu DP, Li L, Han DY. Clinical efficacy of dendritic cells combined with cytokine killer cells in treatment of elderly patients with advanced gastric cancer. Clin J Med
2015; 43(2): 132–5.
Zhang Y, Yi SM, Wu ZX. Efficacy of cytokine induced killer cells with dendritic cells biological treatment and chemotherapy for patients with gastric cancer underwent surgery. Chin J Clin Oncol Rehabil
Woo A, Fu T, Popovic M, Chow E, Cella D, Wong CS, Lam H, Pulenzas N, Lechner B, Vuong S, Ganesh V, Bottomley A. Comparison of the EORTC STO-22 and the FACT-Ga quality of life questionnaires for patients with gastric cancer. Ann Palliat Med
2016; 5(1): 13–21.
Relvas-Silva M, Silva RA, Dinis-Ribeiro M. Portuguese version of the EORTC QLQ-OES18 and QLQ-OG25 for health-related quality of life assessment. Acta Med Port
2017; 30(1): 47–52.
Chen XZ, Zhang WK, Yang K, Wang LL, Liu J, Wang L, Hu JK, Zhang B, Chen ZX, Chen JP, Zhou ZG, Mo XM. Correlation between serum CA724 and gastric cancer: multiple analyses based on Chinese population. Mol Biol Rep
2012; 39(9): 9031–9.
Shen M, Wang H, Wei K, Zhang J, You C. Five common tumor biomarkers and CEA for diagnosing early gastric cancer: a protocol for a network meta-analysis of diagnostic test accuracy. Medicine (Baltimore)
2018; 97(19): e0577.
Emoto S, Ishigami H, Yamashita H, Yamaguchi H, Kaisaki S, Kitayama J. Clinical significance of CA125 and CA72-4 in gastric cancer with peritoneal dissemination. Gastric Cancer
2012; 15(2): 154–61.
Fan B, Xiong B. Investigation of serum tumor markers in the diagnosis of gastric cancer. Hepatogastroenterology
2011; 58(105): 239–45.
Liu X, Sheng W, Wang Y. An analysis of clinicopathological features and prognosis by comparing hepatoid adenocarcinoma of the stomach with AFP-producing gastric cancer. J Surg Oncol
2012; 106(3): 299–303.
Ma QB, Li GX, Wang WH, Li A, Xue KW, Fu JK. Clinical curative effect of the autogenous DC-CIK cells in treating advanced stomach cancer. Qingdao Med J
2015; 47(2): 98–100.
Zhang ZQ, Wang ZY, Zheng S, Wang XZ, He LJ. Efficacy of DC-CIK cell immunotherapy combined with Tegafur chemotherapy in the treatment of advanced gastric cancer in the elderly. Chin J Mod Drug Appl
2016; 3: 144–5.
Liu XL, Dong M, Guo HY, Tang YL, Han JZ, Cui DH. Clinical efficiency observation of dendritic cells and cytokine-induced killer cells combination therapy on advanced gastric cancer patients. Chin J Surg Integr Tradit West Med
2016; 22(2): 124–7.
Shimada H, Noie T, Ohashi M, Oba K, Takahashi Y. Clinical significance of serum tumor markers for gastric cancer: a systematic review of literature by the Task Force of the Japanese Gastric Cancer Association. Gastric Cancer
2014; 17(1): 26–33.
Kissick HT, Sanda MG, Dunn LK, Pellegrini KL, On ST, Noel JK, Arredouani MS. Androgens alter T-cell immunity by inhibiting T-helper 1 differentiation. Proc Natl Acad Sci U S A
2014; 111(27): 9887–92.
Wang ZX, Cao JX, Wang M, Li D, Cui YX, Zhang XY, Liu JL, Li JL. Adoptive cellular immunotherapy for the treatment of patients with breast cancer: a meta-analysis. Cytotherapy
2014; 16(7): 934–45.
Dulos J, Carven GJ, van Boxtel SJ, Evers S, Driessen-Engels LJ, Hobo W, Gorecka MA, de Haan AF, Mulders P, Punt CJ, Jacobs JF, Schalken JA, Oosterwijk E, van Eenennaam H, Boots AM. PD-1 blockade augments Th1 and Th17 and suppresses Th2 responses in peripheral blood from patients with prostate and advanced melanoma cancer. J Immunother
2012; 35(2): 169–78.
Introna M, Franceschetti M, Ciocca A, Borleri G, Conti E, Golay J, Rambaldi A. Rapid and massive expansion of cord blood-derived cytokine-induced killer cells: an innovative proposal for the treatment of leukemia relapse after cord blood transplantation. Bone Marrow Transplant
2006; 38(9): 621–7.
Li Y, Schmidt-Wolf IG, Wu YF, Huang SL, Wei J, Fang J, Huang K, Zhou DH. Optimized protocols for generation of cord blood-derived cytokine-induced killer/natural killer cells. Anticancer Res
2010; 30(9): 3493–9.
Niu Q, Wang W, Li Y, Qin S, Wang Y, Wan G, Guan J, Zhu W. Cord blood-derived cytokine-induced killer cells biotherapy combined with second-line chemotherapy in the treatment of advanced solid malignancies. Int Immunopharmacol
2011; 11(4): 449–56.
Introna M, Pievani A, Borleri G, Capelli C, Algarotti A, Mico C, Grassi A, Oldani E, Golay J, Rambaldi A. Feasibility and safety of adoptive immunotherapy with CIK cells after cord blood transplantation. Biol Blood Marrow Transplant
2010; 16(11): 1603–7.
Milasiene V, Stratilatovas E, Norkiene V. The importance of T-lymphocyte subsets on overall survival of colorectal and gastric cancer patients. Medicina (Kaunas)
2007; 43(7): 548–54.
Cho MY, Joh YG, Kim NR, Jung SI, Bae JW, Kim YC, Koo BH, Whang CW, Suh SO. Tlymphocyte subsets in patients with AJCC stage III gastric cancer during postoperative adjuvant chemotherapy. American Joint Committee on Cancer. Scand J Surg
2002; 91(2): 172–7.
Wang Y, Xu Z, Zhou F, Sun Y, Chen J, Li L, Jin H, Qian Q. The combination of dendritic cells-cytotoxic T lymphocytes/cytokine-induced killer (DC-CTL/CIK) therapy exerts immune and clinical responses in patients with malignant tumors. Exp Hematol Oncol
2015; 4(1): 32.
Dahlberg CI, Sarhan D, Chrobok M, Duru AD, Alici E. Natural killer cell-based therapies targeting cancer: possible strategies to gain and sustain anti-tumor activity. Front Immunol
Zhang Z, Zhao X, Zhang T, Wang L, Yang L, Huang L, Li F, Liu J, Yue D, Wang F, Li J, Guan F, Xu Y, Zhang B, Zhang Y. Phenotypic characterization and anti-tumor effects of cytokine-induced killer cells derived from cord blood. Cytotherapy
2015; 17(1): 86–97.
Zhang Q, Wang L, Luo C, Shi Z, Cheng X, Zhang Z, Yang Y, Zhang Y. Phenotypic and functional characterization of cytokine-induced killer cells derived from preterm and term infant cord blood. Oncol Rep
2014; 32(5): 2244–52.
Wang L, Wan R, Chen C, Su R, Li Y. Study on clinical efficacy of chemotherapy combined with DC-CIK on the patients with advanced gastric cancer and its influence on immune function. Mod J Integr Tradit Chin West Med
2016; 25(21): 2303–9.
Bie J, Liu K, Zhang YH, Feng G, Fu X, Zhang XP, Wen SM. Clinical efficacy of dendritic cell cytokine–induced killer cells combined with chemotherapy on advanced gastric carcinoma. Mod Oncol
2016; 24(22): 3595–7.
Wu FB, Huang W, Wang KX, Wang MY, Xu FG, Huang CK, Wang X. Study on DC-CIK combined with chemotherapy in the treatment of patients with advanced gastric cancer. Mod J Integr Tradit Chin West Med
2015; 24(3): 242–80.
Lv G, Zhang QJ, Shi YQ, Cao ZY. Clinical observation of chemotherapy combined with autologous cytokine-induced killer cells and dendritic cells for advanced gastric cancer. Med J Chin Peoples Liberation Army
2015; 40(6): 475–8.
Cai JX, Wu JC, Wang B, Tan J. Short-term curative efficacy of DC-CIK cell-therapy combined with chemotherapy on patients with advanced gastric cancer. Acta Univ Med Nanjing
2014; 34(1): 36–40.
Giuliano AE, Connolly JL, Edge SB, Mittendorf EA, Rugo HS, Solin LJ, Weaver DL, Winchester DJ, Hortobagyi GN. Breast Cancer-Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin
2017; 67(4): 290–303.
Smith HR. Depression in cancer patients: pathogenesis, implications and treatment (Review). Oncol Lett
2015; 9(4): 1509–14.
Misono S, Weiss NS, Fann JR, Redman M, Yueh B. Incidence of suicide in persons with cancer. J Clin Oncol
2008; 26(29): 4731–8.