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      OncoTargets and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the pathological basis of cancers, potential targets for therapy and treatment protocols to improve the management of cancer patients. Publishing high-quality, original research on molecular aspects of cancer, including the molecular diagnosis, since 2008. Sign up for email alerts here. 50,877 Monthly downloads/views I 4.345 Impact Factor I 7.0 CiteScore I 0.81 Source Normalized Impact per Paper (SNIP) I 0.811 Scimago Journal & Country Rank (SJR)

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      Clinical applications of dendritic cells–cytokine-induced killer cells mediated immunotherapy for pancreatic cancer: an up-to-date meta-analysis

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Purpose

          This study aimed to systematically evaluate the efficacy and safety of dendritic cells–cytokine-induced killer (DC–CIK) cells immunotherapy in treating pancreatic cancer (PC) patients.

          Methods

          Data were collected from published articles of clinical trials. Databases including Web of Science, EMBASE, PubMed, Cochrane Library, Wanfang, and CNKI were searched. The main outcome measures in this research included the overall response rate (ORR), disease control rate (DCR), overall survival (OS), patients’ quality of life (QoL), immune function, and adverse events. Comparative analysis was conducted between DC–CIK immunotherapy and chemotherapy (combined therapy) and chemotherapy alone.

          Results

          This analysis covered 14 trials with 1,088 PC patients involved. The combined therapy showed advantages over chemotherapy alone in ORR (odds ratio [OR] =1.69, 95% confidence interval [CI] =1.20–2.38, P=0.003), DCR (OR =2.33, 95% CI =1.63–3.33, P<0.00001), OS (1-year OS, OR =3.61, 95% CI =2.41–5.40, P<0.00001; 3-year OS, OR =2.65, 95% CI =1.56–4.50, P=0.0003) and patients’ QoL ( P<0.01) with statistical significance. After immunotherapy, lymphocyte subsets’ percentages of CD3 + ( P<0.00001), CD4 + ( P=0.01), CD3 +CD56 + ( P<0.00001), and cytokine levels of IFN-γ ( P<0.00001) were significantly increased, and the percentages of CD4 +CD25 +CD127 low ( P<0.00001) and levels of IL-4 ( P<0.0001) were significantly decreased, whereas analysis on CD8 + ( P=0.59) and CD4 +/CD8 + ratio ( P=0.64) did not show a significant difference.

          Conclusion

          The combination of DC–CIK immunotherapy and chemotherapy is effective for PC treatment, indicated by prolonging the PC patients’ survival time, which benefit from reconstructed immune function of patients.

          Most cited references34

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          Quantifying the impact of between-study heterogeneity in multivariate meta-analyses

          Measures that quantify the impact of heterogeneity in univariate meta-analysis, including the very popular I 2 statistic, are now well established. Multivariate meta-analysis, where studies provide multiple outcomes that are pooled in a single analysis, is also becoming more commonly used. The question of how to quantify heterogeneity in the multivariate setting is therefore raised. It is the univariate R 2 statistic, the ratio of the variance of the estimated treatment effect under the random and fixed effects models, that generalises most naturally, so this statistic provides our basis. This statistic is then used to derive a multivariate analogue of I 2, which we call . We also provide a multivariate H 2 statistic, the ratio of a generalisation of Cochran's heterogeneity statistic and its associated degrees of freedom, with an accompanying generalisation of the usual I 2 statistic, . Our proposed heterogeneity statistics can be used alongside all the usual estimates and inferential procedures used in multivariate meta-analysis. We apply our methods to some real datasets and show how our statistics are equally appropriate in the context of multivariate meta-regression, where study level covariate effects are included in the model. Our heterogeneity statistics may be used when applying any procedure for fitting the multivariate random effects model. Copyright © 2012 John Wiley & Sons, Ltd.
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            Randomized selection design trial evaluating CD8+-enriched versus unselected tumor-infiltrating lymphocytes for adoptive cell therapy for patients with melanoma.

            Adoptive cell therapy (ACT) with autologous tumor-infiltrating lymphocytes (TILs) and high-dose interleukin-2 (IL-2) administered to lymphodepleted patients with melanoma can cause durable tumor regressions. The optimal TIL product for ACT is unknown. Patients with metastatic melanoma were prospectively assigned to receive unselected young TILs versus CD8(+)-enriched TILs. All patients received lymphodepleting chemotherapy and high-dose IL-2 therapy and were assessed for response, toxicity, survival, and immunologic end points. Thirty-four patients received unselected young TILs with a median of 8.0% CD4(+) lymphocytes, and 35 patients received CD8(+)-enriched TILs with a median of 0.3% CD4(+) lymphocytes. One month after TIL infusion, patients who received CD8(+)-enriched TILs had significantly fewer CD4(+) peripheral blood lymphocytes (P = .01). Twelve patients responded to therapy with unselected young TILs (according to Response Evaluation Criteria in Solid Tumors [RECIST]), and seven patients responded to CD8(+)-enriched TILs (35% v 20%; not significant). Retrospective studies showed a significant association between response to treatment and interferon gamma secretion by the infused TILs in response to autologous tumor (P = .04), and in the subgroup of patients who received TILs from subcutaneous tumors, eight of 15 patients receiving unselected young TILs responded but none of eight patients receiving CD8(+)-enriched TILs responded. A randomized selection design trial was feasible for improving individualized TIL therapy. Since the evidence indicates that CD8(+)-enriched TILs are not more potent therapeutically and they are more laborious to prepare, future studies should focus on unselected young TILs.
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              Phase I Study of Random Healthy Donor-Derived Allogeneic Natural Killer Cell Therapy in Patients with Malignant Lymphoma or Advanced Solid Tumors.

              Natural killer (NK) cells with mismatched killer cell immunoglobulin-like receptor-ligand pairs have shown efficacy and been proven safe in treatment of cancer patients. Ex vivo-expanded and highly activated NK cells (MG4101) had been generated under good manufacturing practice conditions, which demonstrated potent anticancer activity in vitro and in vivo in preclinical studies. The current phase I clinical trial was designed to evaluate safety and possible clinical efficacy of repetitive administrations of MG4101 derived from random unrelated healthy donors into patients with malignant lymphoma or advanced, recurrent solid tumors. The maximum dose (3 × 10(7) cells/kg, triple infusion) was tolerable without significant adverse events. Of 17 evaluable patients, 8 patients (47.1%) showed stable disease and 9 (52.9%) showed progressive disease. We also evaluated the capacity of MG4101 to influence host immune responses. Administration of MG4101 augmented NKG2D expression on CD8(+) T cells and upregulated chemokines that recruit T cells. In contrast, administration of MG4101 reduced regulatory T cells and myeloid-derived suppressor cells and suppressed TGFβ production. In conclusion, administration of a large number of MG4101 cells was not only safe and feasible, but also exhibited efficacy in maintaining the effector arm of the host immune response.
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                Author and article information

                Journal
                Onco Targets Ther
                Onco Targets Ther
                OncoTargets and Therapy
                OncoTargets and therapy
                Dove Medical Press
                1178-6930
                2017
                23 August 2017
                : 10
                : 4173-4192
                Affiliations
                [1 ]Department of Health
                [2 ]Department of Central Laboratory, Liaocheng People’s Hospital of Taishan Medical University, Liaocheng, Shandong
                [3 ]Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
                Author notes
                Correspondence: Kai Qu, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, No 277 West Yan-ta Road, Xi’an 710061, Shaanxi, China, Tel +86 136 0911 7104, Email xajtquk@ 123456126.com
                Ke Li, Department of Central Laboratory, Liaocheng People’s Hospital of Taishan Medical University, Dongchang West Road, No 67, Liaocheng 252000, Shandong, China, Tel +86 152 6356 5765, Email zxsyslk@ 123456163.com
                Article
                ott-10-4173
                10.2147/OTT.S143382
                5574601
                3d51cb42-dbeb-4c5f-976f-cd85b56815be
                © 2017 Zhang et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Oncology & Radiotherapy
                cytokine-induced killer cells,dendritic cells,pancreatic cancer,immunotherapy,meta-analysis

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