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Harnessing cytokine-induced killer cells to accelerate diabetic wound healing:an approach to regulating post-traumatic inflammation

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Regenerative Biomaterials 2024年第2期3卷 88-99页

作者： Yixi Yang Cheng Zhang Yuan Jiang Yijun He iawei Cai Lin Liang Zhaohuan Chen Sicheng Pan Chu Hua Keke Wu Le Wang Zhiyong Zhang Translational Research Centre of Regenerative Medicine and 3D Printing of Guangzhou Medical University Guangdong Province Engineering Research Center for Biomedical EngineeringState Key Laboratory of Respiratory DiseaseDepartment of Orthopaedic SurgeryMedical Technology and Related Equipment Research for Spinal Injury TreatmentCity Key LaboratoryThe Third Affliated Hospital of Guangzhou Medical UniversitySchool of Biomedical EngineeringGuangzhou MedicalUniversityGuangzhouGuangdong510150P.R.China Department of Osteoarthropathy and Sports Medicine Panyu Central HospitalGuangzhou 511400P.R.China

Impaired immunohomeostasis in diabetic wounds prolongs infiammation and cytokine dysfunction,thus,delaying or pre-venting wound-surface *** clinical studies have been conducted on cytokine-induced killer(CIK)cells recently,as they can be easily proliferated using a straightforward,inex-pensive ***,the function of CIK cells in regulat-ing inflammatory environments has been drawing attention for clinical *** the current investigation,we discovered the regenerative capacity of these cells in the chal-lenging environment of wounds that heal poorly due to *** demonstrated that the intravenous injection of CIK cells can re-establish a proregenerative inflammatory *** *** accelerateskin healing in diabetic *** results indicated that CIK cell treatment affects macrophage polarization and restores the function regenerative cells under hyperglycemic *** novel cellular therapy offers a promising intervention for clinical applic tions through specific inflammatory regulation functions.

关键词： macrophage diabetic wound post-traumatic inflammation cytokine-induced killer cells vascularization

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Infusions of recipient-derived cytokine-induced killer cells of donor origin eradicated residual disease in a relapsed leukemia patient after allo-hematopoietic stem cell transplantation

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Chinese Medical Journal 2012年第9期125卷 1669-1671页

作者： ZHONG Zhao-dong LUO Yi ZOU Ping ZHENG Jin-e YAO Jun-xia HUANG Shi-ang ZHOU Dong-feng YOU Yong Department of Hematology Union Hospital of Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei 430022 China Center for Stem Cell Research and Application Union Hospital of Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei 430022 China Department of Pediatric Hematology Union Hospital of Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei 430022 China

A female patient diagnosed with acute myelocytic leukemia M5a （AML-M5a） relapsed 986 days after her allogeneic peripheral blood stem cell transplantation （alIo-PBSCT） from an unrelated male donor with matched human leukocyte antigen （HLA）. Three re-induction chemotherapies were administered, and partial remission was achieved. The patient was given repetitive infusion of cytokine-induced killer （CIK） cells expanded from recipient peripheral mononuclear cells of full donor chimerism due to loss of contact of quondam donor for donor lymphocyte infusion （DLI） and rejection of second transplantation. The patient achieved complete cytogenetical remission. This strategy might overcome the obstacle of donor unavailability and present an appealing new therapeutic alternative to donor-recruited adoptive immunotherapy for relapsed disease at post-transplantation.

关键词： cytokine-induced killer cells stem cell transplantation relapsed leukemia minor residual disease donor lymphocyte infusion

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Cholangiocarcinoma-derived exosomes inhibit the antitumor activity of cytokine-induced killer cells by down-regulating the secretion of tumor necrosis factor-α and perforin

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2016年第7期17卷 537-544页

作者： Jiong-huang CHEN Jian-yang XIANG Guo-ping DING Li-ping CAO Department of General Surgery Sir Run Run Shaw Hospital School of Medicine Zhejiang University

Objective： The aim of our study is to observe the impact of cholangiocarcinoma-derived exosomes on the antitumor activities of cytokine-induced killer （CIK） cells and then demonstrate the appropriate mechanism. Methods： Tumor-derived exosomes （TEXs）, which are derived from RBE cells （human cholangiocarcinoma line）, were collected by ultracentrifugation. CIK cells induced from peripheral blood were stimulated by TEXs. Fluorescence-activated cell sorting （FACS） was performed to determine the phenotypes of TEX-CIK and N-CIK （normal CIK） cells. The concen- trations of tumor necrosis factor-a （TNF-a） and perforin in the culture medium supematant were examined by using an enzyme-linked immunosorbent assay （ELISA） kit. A CCK-8 kit was used to evaluate the cytotoxic activity of the CIK cells to the RBE cell line. Results： The concentrations of TNF-a and perforin of the group TEX-CIK were 138.61 pg/ml and 2.41 ng/ml, respectively, lower than those of the group N-CIK 194.08 pg/ml （P〈0.01） and 3.39 ng/ml （P〈0.05）. The killing rate of the group TEX-CIK was 33.35%, lower than that of the group N-CIK （47,35% （P〈0.01））. The population of CD3＋, CD8＋, NK （CD56＋）, and CD3＋CD56＋ cells decreased in the TEX-CIK group （63.2±6.8）%, （2.5±1.0）%, （0.53±0.49）%, （0.45±0.42）%） compared with the N-CIK group （（90.3±7.3）%, （65.7±3.3）%, （4.2±1.2）%, （15.2±2.7）%）, P〈0.01. Conclusions： Our results suggest that RBE cells-derived exosomes inhibit the antitumor activity of CIK cells by down-regulating the population of CD3＋, CD8＋, NK （CD56＋）, and CD3＋CD56＋ cells and the secretion of TNF-a and perforin. TEX may play an important role in cholangiocarcinoma immune escape.

关键词： Cholangiocarcinoma Tumor-derived exosomes cytokine-induced killer cells Immune escape

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Cisplatin pretreatment enhances anti-tumor activity of cytokine-induced killer cells

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World Journal of Gastroenterology 2011年第25期17卷 3002-3011页

作者： Xiang Huang Yi-Tian Chen Hai-Zhu Song Gui-Chun Huang Long-Bang Chen Department of Medical Oncology MedicalSchool of Nanjing University Jinling Hospital 305 ZhongshanEast Road Nanjing 210002 Jiangsu Province China

AIM： To investigate whether cisplatin （DDP） enhances the anti-tumor activity of cytokine- induced killer （CIK） cells in a murine colon adenocarcinoma model. METHODS： Tumor size and weight served as indicators of therapeutic response. Immunohistochemistry was performed to observe intratumoral lymphocyte infiltration and tumor microvessel density. Changes in the percentage of regulatory T （Treg） cells within the spleens of tumor-bearing mice preconditioned with DDP were monitored using flow cytometry. RESULTS： A marked T cell-dependent, synergistic anti- tumor effect of the combined therapy was observed （1968 ± 491 mm3 ys 3872 ＋ 216 mm3; P = 0,003）, Preconditioning chemotherapy with DDP augmented the infiltration of CD3＋ T lymphocytes into the tumor mass and reduced the percentage of both intratumoral and splenic Treg cells. CONCLUSION： Preconditioning with DDP markedly enhances the efficacy of adoptively transferred CIK cells, providing a potential clinical modality for the treatment of patients with colorectal cancer.

关键词： Colorectal cancer Preconditioning chemo-therapy cytokine-induced killer cells Regulatory Tcells Immunomodulation

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cytokine-induced killer cells in Combination With Transcatheter Arterial Chemoembolization and Radiofrequency Ablation for Hepatocellular Carcinoma Patients

Cytokine-induced Killer Cells in Combination With Transcathe...

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第九届中国肿瘤微创治疗学术大会

作者： Zhi-Mei Huang Wang Li Sheng Li Fei Gao Qi-Ming Zhou Fang-Ming Wu Ni He Chang-Chuan Pan Jian-Chuan Xia Pei-Hong Wu Ming Zhao Division of Medical Imaging and Interventional Radiology Center of Medical Image and Image Guided TherapySun Yat-Sen University Cancer Center State Key Laboratory of Oncology in South China Department of Oncology The 6th People Hospital of Shenzhen Medical Oncology The Second People Hospital of Sichuan

＜正＞This study evaluated the clinical efficacy of autologous cytokine-induced killer（CIK） cell transfusion in combination with transcatheter arterial chemoembolization（TACE） and radio-frequency ablation（RFA）,compared to sequential therapy with TACE and RFA,for the treatment of hepatocellular carcinoma （HCC）.We retrospectively studied 2 groups of HCC patients:85 patients in the TACE + RFA + CIK group were treated with adoptive autologous CIK cell transfusion in combination with minimally invasive therapy,89 patients in the TACE + RFA group were treated with minimally invasive therapy *** overall response rate was 76.5%in the TACE + RFA + CIK group and 79.8%in the TACE + RFA *** disease control rate was higher in the TACE + RFA + CIK group than that in the TACE + RFA group（95.3%vs.88.8%）,but the difference was not significant（P=0.113）.Kaplan-Meier analysis showed that the patients in the TACE + RFA + CIK group had significantly longer overall survival（56 vs.31 mo,P—0.001） and progression-free survival（17 vs.10mo,P = 0.001） than those in the TACE + RFA *** severe side effects occurred in the CIK cell transfusion *** conclusion,CIK cell immunotherapy may be a valuable therapeutic strategy to prevent recurrence and metastasis in HCC patients after TACE and RFA,and to improve patient prognosis and quality of *** CIK immunotherapy and minimally invasive therapies represent a safe,potential treatment modality for ***,because patient assignment to the 2 treatments was not randomized,any conclusions concerning improvements in survival must be interpreted with great caution.

关键词： hepatocellular carcinoma minimally invasive therapy transcatheter arterial chemoembolization radiofrequency ablation cytokine-induced killer cells overall survival progression-free survival

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Anti-tumour activity of cytokine-induced killer cells co-cultured with autologous dendritic cells transfected with tumor total RNA against hormone-refractory prostate cancer (HRPC) in vitro

Anti-tumour activity of cytokine-induced killer cells co-cul...

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第十三届全国泌尿外科学术会议暨第八届全球华人泌尿外科学术会议

作者： Jun Pang, Xin Gao, Hailun Zhan, Kebing Wang, Xiaopeng Liu, Xingqiao Wen, Youqiang Fang, Yubin Cai. department of urology, the third affiliated hospital of Sun Yat-sen university, Tianhe Road 600,Guangzhou city, Guangdong Province,510630

Objective: To investigate the efficacy of CIK co-cultured with autologous DC transfected with tumor RNA derived from hormone-insensitive prostate cancer cell lines PC3 and DU145, induce polyclonal prostate cancer-spec... 详细信息

关键词： dendritic cells cytokine-induced killer cells hormone-refractory prostate cancer

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Effectiveness and safety of cytokine-induced killer cells cocultured with dendritic cells treatment in colorectal cancer

Effectiveness and safety of cytokine-induced killer cells co...

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第十届全国免疫学学术大会

作者： Yanqiu Fang Haifeng Wei Zhiqiang Ni Junjie Hou Duo Liu Yuyang Zhang Xianzhuo Jiang Yan Tan 吉林省人民医院

Objective:To evaluate efficacy and safety of dendritic cells in combination with cytokine-induced killer cell treatment of patients with colorectal ***:113 colorectal patients were enrolled in this study.61 patients accepted DC-CIK cells treatment on the basis of chemotherapy were defined as‘CIK group’and the other 52 patients accepted chemotherapy alone were defined as‘Con-trol group’.The short-term clinical curative effects and survival rate were compared between two *** host cellular immune function,quality of life(QOL)and hematological markers including serum levels of tumor markers,ratio of neutrophils to lymphocytes(N/L ratio)and levels of serum adenosine deaminase(ADA)before and after therapy were comparatively ***:The disease control rate(DCR)was significantly higher in CIK group than in the control group(P=0.045)and more biotherapies(>2 cycle)could benefit patients in higher DCR compared with fewer biotherapies(1 cycle)(P=0.022).No statistically significant difference was found in the overall survival between the two groups(P=0.254),whereas compared to patients in the control group,the patients in CIK group had significantly longer progression-free survival(P=0.018).The ratio of neutrophils to lymphocytes(N/L ratio)was significantly lower in CIK group than in the control group(2.74±1.31 vs.2.32±0.98,P=0.046).The serum levels of tumor markers,including CA19-9,CA24-2 and CEA,were significantly decreased after DC-CIK cells *** host immune function was enhanced and QOL was improved in the patients treated by DC-CIK biotherapy compared to the patients treated by chemotherapy *** most common side effects were fever(15.8%),chill(8.8%),headache(5.3%),nausea and vomiting(5.3%)and skin rash(1.8%).No severe side effects occurred in the DC-CIK cells transfusion patients and no toxic reaction resulted from DCCIK cells ***:DC-CIK immunotherapy is a potential effective and safe approach for patients with colo

关键词： Colorectal cancer Dendritic cells cytokine-induced killer cells Immunotherapy Clinical research

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Effect of dendritic cell-cytokine induced killer cells in patients with triple-negative breast cancer

Effect of dendritic cell-cytokine induced killer cells in pa...

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第十一届全国免疫学学术大会

作者： Xie Yunqing Liu Jian Lin Xiaowei Liu Shijia Ying Mingang Zheng Qiuhong Fujian Provincial Key Laboratory of Tumor Biotherapy

Purpose: Triple-negative breast cancer(TNBC) is a breast cancer type with poor prognosis due to the absence of targets for the treatment of endocrine and anti-HER-2 therapy. Furthermore, only about 20% of TNBC are sensitive to conventional chemotherapy. Therefore, this study aimed to evaluate the clinical efficacy of adjuvant dendrtic cell(DC)-cytokineinduced killer cells(CIK) immunotherapy combined with chemotherapy with/without radiotherapy in patients with postoperative ***: From December 1,2006 to February28,2011, 68 patients with postoperative TNBC were included in this retrospective study: 43 cases received chemotherapy with/without radiotherapy;25 cases received DC-CIK cells infusion combined with chemotherapy with/without ***: Survival analysis showed the 5-years disease-free survival(DFS) rate was significantly higher in the DC-CIK group compared with the non- DC-CIK group(P=0.049). Further subgroup analysis stratified according to tumor–node–metastasis(TNM) stages showed that the 5-years DFS was significantly increased in DC-CIK group with advanced TNM stages(including IIb,III,IV TNM stage) than the non- DC-CIK, and 5-year OS rate in advanced-stage subgroup was also improved although it only approved borderline statistical significance(P=0.051).Conclusions: Our results demonstrated that TNBC patients with advanced TNM stages could benefitted from adjuvant DC-CIK cells infusion combined with conventional therapy in terms of preventing disease relapse and increasing overall survival.

关键词： dendritic cells cytokine-induced killer cells adjuvant immunotherapy triple-negative breast cancer

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Effective activity of cytokine induced killer cells against hepatocellular carcinoma including tumor-initiating cells

Effective activity of cytokine induced killer cells against ...

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第十四届全国肿瘤生物治疗大会

作者： Xiaoxiang Fang Aimin Li Dong Rongcheng Department of Oncology Nanfang Hospital Southern Medical University Cancer Research Institute Southern Medical University

Tumor-initiating cells(TICs) are a subpopulation of chemoresistant tumor cells that have been shown to cause tumor recurrence. Targeting and eliminating of TICs are therefore priorities for the development of new therapeutic paradigms. Much promise lies in adoptive immunotherapy. cytokine-induced killer(CIK) cells are heterogeneous ex vivo-expanded T lymphocytes, with a mixed T-NK phenotype. It represents a realistic new option in the field of Hepatocellular carcinoma(HCC) immunotherapy. In the very recent years, Large clinical trials demonstrated that CIK cells could improve the Progression Free Survival(PFS) and Overall Survival(OS) in patients with HCC. By the same time, several studies reported that CIK cells were capable of clearing cells with stemness features in Lymphoma, Melanoma, Bone and Soft-Tissue Sarcomas. Based on the findings above mentioned, we hypothesized that CIK cells could eliminate the tumor-initiating cells, improving the PFS and OS of patients with HCC when combined with radiofrequency ablation(RFA) or transcatheter arterial chemoembolization(TACE).

关键词： hepatocellular carcinoma cytokine-induced killer cells tumor-initiating cells

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Dendritic cell-cytokine induced killer cells infusion prolongs overall and progression-free survival rates in advanced colorectal cancer

Dendritic cell-cytokine induced killer cells infusion prolon...

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第十四届全国肿瘤生物治疗大会

作者： YunQing Xie QiuHong Zheng LiJie Huang XiaoWei Lin ShiJia Liu ShanShan Chen 福建省肿瘤医院

Purpose: To evaluate the activity of dendritic cells-cytokine induced killer(DCs-CIK) cells infusion as an adjuvant therapy for colorectal carcinoma patients combined with first-line treatment. Methods: A total of 142 patients with stage III/IV colorectal carcinoma who treated with first-line therapy were studied retrospectively. Among them, 71 patients received first-line treatment, another 71 patients received DC-CIK cells infusion combined with first-line treatment. These patients were followed up until Aug. 2014. Data were analyzed by Kaplan-Meier and Cox regression. Results: Our results showed that the 5-years overall survival(OS) rate for the DC-CIK group versus non-DC-CIK group was 41.3% versus 19.4%,(P=0.001). In addition, the 5-years progression-free survival(PFS) rate was 57.4% versus 33.6%,(P= 0.022), respectively. Conclusion: DC-CIK immunotherapy combined with first-line therapy significantly prolongs 5-year OS and 5-year PFS for advanced colorectal cancer.

关键词： dendritic cells cytokine-induced killer cells adjuvant immunotherapy colorectal cancer

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