Immunotherapy with dendritic cells and cytokine-induced killer cells for hepatocellular carcinoma: A meta-analysis

BACKGROUND Hepatocellular carcinoma(HCC) has been revealed as the second most common cause of cancer-related deaths worldwide. The introduction of cell-based immunotherapy, including dendritic cells(DCs) and cytokine-induced killer cells(CIKs), has brought HCC patients an effective benefit. However, the efficacy and necessity of cellular immunotherapy after different interventional therapy remains to be further explored.AIM To investigate the efficacy of cellular immunotherapy, involving DCs and CIKs,combined with different conventional treatments of HCC.METHODS We performed a literature search on PubMed and Web of Science up to February15, 2019. Long-term efficacy(overall survival and recurrence) and short-term adverse effects were investigated to assess the effectiveness of immunotherapy with DCs and/or CIKs. Review Manager 5.3 was used to perform the analysis.RESULTS A total of 22 studies involving 3756 patients selected by eligibility inclusion criteria were forwarded for meta-analysis. Combined with the conventional clinical treatment, immunotherapy with DCs and/or CIKs was demonstrated to significantly improve overall survival at 6 mo [risk ratio(RR) = 1.07; 95%confidence interval(CI): 1.01-1.13, P = 0.02], 1 year(RR = 1.12; 95%CI: 1.07-1.17, P 0.00001), 3 years(RR = 1.23; 95%CI: 1.15-1.31, P 0.00001) and 5 years(RR =1.26; 95%CI: 1.15-1.37, P 0.00001). Recurrence rate was significantly reduced by cellular immunotherapy at 6 mo(RR = 0.50; 95%CI: 0.36-0.69, P 0.0001) and 1 year(RR = 0.82; 95%CI: 0.75-0.89, P 0.00001). Adverse effect assessment addressed that immunotherapy with DCs and/or CIKs was accepted as a safe,feasible treatment.CONCLUSION Combination immunotherapy with DCs, CIKs and DC/CIK with various routine treatments for HCC was evidently suggested to improve patients' prognosis by increasing overall survival and reducing cancer recurrence.     

Dendritic cell-based cancer immunotherapy for pancreatic cancer

Pancreatic cancer (PC) is a lethal disease and remains one of the most resistant cancers to traditional therapies. New therapeutic modalities are urgently needed, particularly immunotherapy, which has shown promise in numerous animal model studies. Dendritic cell (DC)-based immunotherapy has been used in clinical trials for various cancers, including PC, because DCs are the most potent antigen-presenting cell (APC), which are capable of priming naive T cells and stimulating memory T cells to generate antigen-specific responses. In this paper, we review the preclinical and clinical efforts towards the application of DCs for PC.     

Combination treatment with comprehensive cryoablation and immunotherapy in metastatic hepatocellular cancer

AIM: To retrospectively assess the effect of comprehensive cryosurgery (ablation of intraand extra-hepatic tumors) plus dendritic cell-cytokine-induced killer cell immunotherapy in metastatic hepatocellular cancer. METHODS: We divided 45 patients into cryo-immunotherapy (21 patients), cryotherapy (n = 12), immunotherapy (n = 5) and untreated (n = 7) groups. Overall survival (OS) after diagnosis of metastatic hepatocellular cancer was assessed after an 8-year follow-up. RESULTS: Median OS was higher following cryo-immu-notherapy (32 mo) or cryotherapy (17.5 mo; P < 0.05) than in the untreated group (3 mo) and was higher in the cryo-immunotherapy group than in the cryotherapy group (P < 0.05). In the cryo-immunotherapy group, median OS was higher after multiple treatments (36.5 mo) than after a single treatment (21 mo; P < 0.05). CONCLUSION: Cryotherapy and, especially, cryoimmunotherapy significantly increased OS in metastatic hepatocellular cancer patients. Multiple cryo-immunotherapy was associated with a better prognosis than single cryo-immunotherapy.     

Increasing the frequency of CIK cells adoptive immunotherapy may decrease risk of death in gastric cancer patients

AIM: To analyze the correlation between cytokineinduced killer (CIK) cells adoptive immunotherapy and cancer-related death in gastric cancer patients. METHODS: One hundred and fifty-six gastric cancer patients after operation at the Third Affiliated Hospital of Soochow University were enrolled in this study. Their clinical data including demographic characteristics, operation time, tumor size, pathological type and staging, tumor metastasis, outcome of chemotherapy or CIK cells adoptive immunotherapy, survival time or time of death were collected with a standard structured questionnaire. Kaplan-Meier method was used to estimate the median survival time, and the 2- and 5- year survival rates. Hazard risk (HR) and 95% confidence interval (95% CI) of CIK cells adoptive immunotherapy for gastric cancer were calculated using the two-stage time-dependent covariates Cox model. RESULTS: The survival time of gastric cancer patients was longer after CIK cells adoptive immunotherapy than after chemotherapy (χ 2 = 10.907, P = 0.001). The median survival time of gastric cancer patients was also longer after CIK cells adoptive immunotherapy than after chemotherapy (49 mo vs 27 mo, P < 0.05). The 2- and 5-year survival rates of gastric cancer patients were significantly higher after CIK cells adoptive immunotherapy than after chemotherapy (73.5% vs 52.6%, 40.4% vs 23.9%, P < 0.05). A significant difference was observed in the survival curve for patients who received CIK cells adoptive immunotherapy (0, 1-10, 11-25, and over 25 frequencies) (χ 2 = 14.534, P = 0.002). The frequencies of CIK cells adoptive immunotherapy were significantly related with the decreasing risk of death in gastric cancer patients after adjustment for sex and age of the patients, tumor stage and relapse (HR = 0.54, 95% CI: 0.36-0.80) when the first stage Cox model was used to define the subjects who remained alive beyond 36 mo as survivors. However, no correlation was observed between the frequencies of death in CIK cells adoptive immunotherapy a     

An effective vaccine against colon cancer in mice： Use of recombinant adenovirus interleukin-12 transduced dendritic cells

AIM： To investigate the effect of a vaccine with recombinant adenovirus interleukin-12 （AdVIL-12） transduced dendritic cells （DCs） against colon cancer in mice. METHODS： DCs and AdVIL-12 were incubated together at different time intervals and at different doses. Supernatant was collected and tested for IL-12 by enzyme-linked immunosorbent assay （ELISA）. In order to determine whether tumor cell lysate-pulsed （TP） AdVIL-12/DCs enhance therapeutic potential in the established tumor model, CT26 colon tumor cells were implanted subcutaneously （s.c.） in the midflank of naive BALB/c mice. Tumor-bearing mice were injected with a vaccination of CT26 TP AdVIL-12/DCs on d 3 and 10. As a protective colon tumor model, naive BALB/c mice were immunized s.c. in their abdomens with CT26 TP AdVIL-12/DCs twice at seven day intervals. After the immunization on d 7, the mice were challenged with a lethal dose of CT26 tumor cells and survival times were evaluated. Subsequently, cytotoxic T lymphocyte （CTL） activity and interferon gamma （IFNy） secretion was evaluated in the immunized mice, and assayed CTL ex vivo. RESULTS： Murine DCs were retrovirally transduced with AdVIL-12 efficiency, and the AdVIL-12 transduced DCs secreted a high level of IL-12 （AdVIL-12/DCs, 615.27 ± 42.3 pg/mL vs DCs, 46.32 ± 7.29 pg/mL, P 〈 0.05）. Vaccination with CT26 TP AdVIL-12/DCs could enhance anti-tumor immunity against CT26 colon tumor in murine therapeutic models （tumor volume on d 19：CT26 TP AdVIL-12/DCs 107 ± 42 mm^3 vs CT26 TP DCs 383± 65 mm^3, P 〈 0.05） and protective models. Moreover, the CT26 TP AdVIL-12/DC vaccination enhances tumor-specific CTL activity, producing high levels of IFN7 in immunized mice. Ex vivo primed T cells with AdVIL-12/DCs were able to induce more effective CTL activity than in primed T cells with CT26 TP/DCs （E：T = 100：1, 69.49% ± 6.11% specific lysis vs 37.44% ＋ 4.32% specific lysis, P 〈 0.05）.CONCLUSION： Vaccination with recombinant AdVIL-12 transduced DC p     

Gastric cancer and the epoch of immunotherapy approaches

The incidence of gastric cancer(GC) fell dramatically over the last 50 years, but according to IARC-Globocan 2008, it is the third most frequent cause of cancerrelated deaths with a case fatality GC ratio higher than other common malignancies. Surgical resection is the primary curative treatment for GC though the overall 5-year survival rate remains poor(approximately 20%-25%). To improve the outcome of resectable gastric cancer, different treatment strategies have been evaluated such as adjuvant or perioperative chemotherapy. In resected gastric cancer, the addition of radiotherapy to chemotherapy does not appear to provide any additional benefit. Moreover, in metastatic patients, chemotherapy is the mainstay of palliative therapy with a median overall survival of 8-10 mo and objective response rates of merely 20%-40%. Therefore, the potential for making key beneficial progress is to investigate the GC molecular biology to realize innovative therapeutic strategies, such as specific immunotherapy. In this review, we provide a panoramic view of the different immune-based strategies used for gastric cancer treatment and the results obtained in the most significant clinical trials. In detail, firstly we describe the therapeutic approaches that utilize the monoclonal antibodies while in the second part we analyze the cell-based immunotherapies.     

树突状细胞联合细胞因子诱导的杀伤细胞对胃癌细胞杀伤作用

目的探讨树突状细胞联合细胞因子诱导的杀伤细胞对胃癌细胞的杀伤作用。方法采用胃癌患者自身血液中单个核细胞(peripheral blood mononuclear cells,PBMC),经体外诱导分别扩增出DC和CIK细胞,二者共同培养后,利用MTT法检测DC细胞联合CIK细胞体外杀伤人胃癌细胞株(MNK-45、MNK-28、SG-7901)的活性。结果DC与CIK细胞共培养后得到的细胞群高表达CD3 CD56 ,平均值达到(56.74±7.63)%。通过彼此相互作用诱导出的细胞群体对胃癌细胞株MNK-45、MNK-28、SG-7901有杀伤作用,且杀伤活性随着效靶比的增加而增强。结论DC与CIK细胞共培养后有很强的增殖能力,对胃癌细胞具有杀伤活性,且其杀伤作用与胃癌细胞类型无相关性。     

Cytokine-induced killer cells/dendritic cells and cytokine-induced killer cells immunotherapy for the treatment of esophageal cancer: A meta-analysis

Objectives:This meta-analysis was designed to systematically evaluate whether autologous cytokine-induced killer cells (CIK) or dendritic cells and cytokine-induced killer cells (DC-CIK) immunotherapy combined with chemotherapy can improve the therapeutic effect and safety of chemotherapy in esophageal cancer (EC).Materials and methods:Randomized controlled trials (RCTs) were electronically searched databases including CNKI, WanFang, WeiPu, CBMDisc, PubMed, Web of Science, EMbase, the Cochrane Library, and Clinical Trials. The databases were searched for articles published until June 2019. Two researchers independently screened the literature, extracted data, and evaluated the quality of the included literature. Meta-analysis was performed using RevMan5.3.Results:Seventeen studies (1416 participants) were included. The differences between CIK/DC-CIK combination chemotherapy and chemotherapy alone were significant. The results displayed that the number of CD3⁺, CD4⁺, CD4⁺/CD8⁺, and NK cells was significantly increased after 1 to 2 weeks of treatment with CIK/DC-CIK cells in the treatment group (all P < .05). In addition, the results shown that 1-year overall survival was significantly prolonged (P < .0001) and quality of life was improved (P = .001) in EC chemotherapy combined with immunotherapy groups compared with conventional treatment. Furthermore, cytokine expression levels of interleukin 2 (IL-2), tumor necrosis factor α (TNF-α), and interleukin 12 (IL-12) were significantly increased (P = .0003) as well as the levels of immunoglobulins were elevated (P < .00001). Serum levels of tumor marker molecules, carcinoembryonic antigen (CEA), carbohydrate antigen (CA)-199, and CA-125 were lower in treatment groups than that of control groups (P < .00001). No fatal adverse reactions were noted (P = .04).Conclusions:It is safe and effective for patients to use chemotherapy combined with CIK/DC-CIK immunotherapy. Immunotherapy can simultaneously improve the antitumor immune response. Specifically, DC-CIK cells can increase T lymphocyte subsets, CIK cells, NK cells, and immunoglobulins in peripheral blood to enhance antitumor immunity. Therefore, combination therapy enhances the immune function and improves the therapeutic efficacy of patients with EC.     

Gastrointestinal cancer stem cells as targets for innovative immunotherapy

The role of cancer stem cells in gastrointestinal cancer-associated death has been widely recognized. Gastrointestinal cancer stem cells(GCSCs) are considered to be responsible for tumor initiation, growth, resistance to cytotoxic therapies,recurrence and metastasis due to their unique properties. These properties make the current therapeutic trials against GCSCs ineffective. Moreover, recent studies have shown that targeting stem cell surface markers or stemness associated pathways might have an additional off-target effect on the immune system.Recent advances in oncology and precision medicine have opened alternative therapeutic strategies in the form of cancer immunotherapy. This approach differs from classical anti-cancer therapy through its mechanism of action involving the activation and use of a functional immune system against tumor cells, instead of aiming physically destruction of cancer cells through radio-or chemotherapy. New immunological approaches for GCSCs targeting involve the use of different immune cells and various immune mechanisms like targeting specific surface antigens, using innate immune cells like the natural killer and T cells, T-cell chimeric antigen receptor technology, dendritic cell vaccine, or immune checkpoint inhibitors. In this respect, better understandings of immune regulatory mechanisms that govern anti-tumor response bring new hope in obtaining long-term remission for cancer therapy.     

Neoadjuvant chemotherapy for advanced gastric cancer: a meta-analysis

AIM:To study the value of neoadjuvant chemotherapy (NAC) for advanced gastric cancer by performing a meta-analysis of the published studies.METHODS:All published controlled trials of NAC for advanced gastric cancer vs no therapy before surgery were searched.Studies that included patients with metastases at enrollment were excluded.Databases included Cochrane Library of Clinical Comparative Trials,MEDLINE,Embase,and American Society of Clinical Oncology meeting abstracts from 1978 to 2010.The censor date was...     

完整结肠系膜切除术后DC-CIK联合奥沙利铂、卡培他滨治疗结肠癌对免疫水平的影响

目的 分析完整结肠系膜切除术后树突状细胞-细胞因子诱导杀伤细胞(DC-CIK cell)联合奥沙利铂、卡培他滨治疗结肠癌的临床效果.方法 回顾性分析2016年1月至2019年1月湖南省郴州市第一人民医院收治的128例结肠癌患者,按不同治疗方法分为两组,对照组54例,完整结肠系膜切除术后经奥沙利铂、卡培他滨治疗;观察组7...     

Effectiveness of 5-flurouracil-based neoadjuvant chemotherapy in locally-advanced gastric/gastroesophageal cancer: A meta-analysis

AIM:To investigate the effectiveness of 5-flurouracilbased neoadjuvant chemotherapy(NAC) for gastroesophageal and gastric cancer by meta-analysis.METHODS:MEDLINE and manual searches were performed to identify all published randomized controlled trials(RCTs) investigating the efficacy of the flurouracilbased NAC for gastroesophageal and gastric cancer,and RCTs of NAC for advanced gastroesophageal and gastric cancer vs no therapy before surgery.Studies that included patients with metastases at enrollment were excluded.Primary endpoint was the odds ratio(OR) for improving overall survival rate of patients with gastroesophageal and gastric cancer.Secondary endpoints were the OR of efficiency for down-staging tumor and increasing R0 resection in patients with gas-troesophageal and gastric cancer.Safety analyses were also performed.The OR was the principal measurement of effect,which was calculated as the treatment group(NAC plus surgery) vs control group(surgery alone) and was presented as a point estimate with 95% confidence intervals(CI).All calculations and statistical tests were performed using RevMan 5.1 software.RESULTS:Seven RCTs were included for the analysis.A total of 1249 patients with advanced gastroesophageal and gastric cancer enrolled in the seven trials were divided into treatment group(n = 620) and control group(n = 629).The quality scores of the RCTs were assessed according to the method of Jadad.The RCT quality scores ranged from 2 to 7(5-point scale),with a mean of 3.75.The median follow-up time in these studies was over 3 years.The meta-analysis showed that NAC improved the overall survival rate(OR 1.40,95%CI 1.11-1.76;P = 0.005),which was statistically significant.The 3-year progression-free survival rate was significantly higher in treatment group than in control group(37.7% vs 27.3%)(OR 1.62,95%CI 1.21-2.15;P = 0.001).The tumor down-stage rate was higher in treatment group than in control group(55.76% vs 41.38%)(OR 1.77,95%CI 1.27-2.49;P = 0.0009) and the R0 resection rate of the gastroesophageal and gastric cancer was higher in treatment group than in control group(75.11% vs 68.56%)(OR 1.38,95%CI 1.03-1.85;P = 0.03),with significant differences.No obvious safety concerns about mortality and complications were raised in these trials.There were no statistically significant differences in perioperative mortality(5.08% vs 4.86%)(OR 1.05,95%CI 0.57-1.94;P = 0.87 fixed-effect model) and in the complication rate between the two groups(13.25% vs 9.66%)(OR 1.40,95%CI 0.91-2.14;P = 0.12 fixed-effect model).Trials showed that patients from Western countries favored NAC compared with those from Asian countries(OR 1.40,95%CI 1.07-1.83).Monotherapy was inferior tomultiple chemotherapy(OR 1.40,95%CI 1.07-1.83).Intravenous administration of NAC was more advantageous than oral route(OR 1.41,95%CI 1.09-1.81).CONCLUSION:Flurouracil-based NAC can safely improve overall survival rate of patients with gastroesophageal/gastric cancer.Additionally,NAC can down the tumor stage and improve R0 resection.     

The safety and efficacy of chemotherapy combined with immunotherapy for pancreatic cancer: A meta-analysis

Background:Since the combination of chemotherapy and immunotherapy, such as new molecular targeted drugs or vaccines, is controversial in terms of survival advantages compared with chemotherapy therapy alone, we conducted a meta-analysis to compare the efficacy and safety of immunotherapy combined with chemotherapy and chemotherapy alone for advanced pancreatic cancer.Methods:We searched PubMed, Embase, and Cochrane Library from the establishment of the database to November 2020. We included some studies that reported pancreatic cancer patients receiving immunotherapy, and we excluded duplicate publications, research without full text, incomplete information or inability to conduct data extraction, animal experiments, reviews, and systematic reviews.Results:The risk ratio of the objective response rate and disease control rate was 1.10 (95% confidence interval [CI]: 0.88–1.38) and 1.17 (95% CI: 1.06–1.31), respectively, indicating that there was no significant difference between the objective response rate of combination therapy and chemotherapy alone, while the disease control rate of the combined treatment was higher than that of chemotherapy alone. The hazard ratio of overall survival and progression-free survival was 0.91 (95% CI: 0.82–1.01) and 0.87 (95% CI: 0.77–0.98), respectively, indicating that there was no significant difference between the overall survival of combination therapy and chemotherapy alone, while progression-free survival of the combined treatment was longer than that of chemotherapy alone. We also found that in addition to the combination treatment, the incidence of vomiting in pancreatic cancer was higher than that of chemotherapy alone, and the incidence of other complications was not significantly different from that of treatment alone.Conclusion:Chemotherapy combined with immunotherapy for pancreatic cancer not only improves treatment efficiency but also does not cause serious adverse reactions. This treatment strategy should be widely used clinically.     

Therapeutic implications of colon cancer stem cells

Colorectal cancer is the second most common cause of cancer-related death in many industrialized countries and is characterized by a heterogenic pool of cells with distinct differentiation patterns. Recently, the concept that cancer might arise from a rare population of cells with stem cell-like properties has received support with regard to several solid tumors, including colorectal cancer. According to the cancer stem cell hypothesis, cancer can be considered a disease in which mutations either convert no...     

Risk of colorectal neoplasm in patients with acromegaly： A meta-analysis

AIM： To examine the risk of colorectal neoplasm in acromegalic patients by meta-analyzing all relevant controlled studies.
METHODS： Extensive English language medical literature searches for human studies, up to December 2007, were performed using suitable keywords. Pooled estimates [odds ratio （OR） with 95% confidence intervals （CI）] were obtained using either the fixed or random-effects model as appropriate. Heterogeneity between studies was evaluated with the Cochran Q test whereas the likelihood of publication bias was assessed by constructing funnel plots. Their symmetry was estimated by the adjusted rank correlation test.
RESULTS： For hyperplastic polyps the pooled ORs with 95% CI were 3.557 （2.587-4.891） by fixed effects model and 3.703 （2.565-5.347） by random effects model. The Z test values for overall effect were 7.81 and 6.984, respectively （P 〈 0.0001）. For colon adenomas the pooled ORs with 95% CI were 2.486 （1.908-3.238） （fixed effects model） and 2.537 （1.914-3.364） （random effects model）. The Z test values were 6.747 and 6.472, respectively （P 〈 0.0001）. For colon cancer the pooled OR with 95% CI was identical for both fixed and random effects model （OR, 4.351; 95% CI, 1.533-12.354; Z = 2.762, P = 0.006]. There was no significant heterogeneity and no publication bias in all the above meta-analyses.
CONCLUSION： Acromegaly is associated with an increased risk of colorectal neoplasm.     

A meta-analysis of randomized controlled trials comparing chemotherapy plus bevacizumab with chemotherapy alone in metastatic colorectal cancer

Purpose  Bevacizumab has demonstrated survival benefit in metastatic colorectal cancer (mCRC) patients when combined with chemotherapy. Several randomized clinical studies have evaluated bevacizumab in combination with chemotherapy. Meta-analysis was performed to better assess the efficacy and safety of bevacizumab with chemotherapy for mCRC. Materials and methods  Five clinical trials randomizing a total of 3,103 mCRC patients to chemotherapy alone or to the combined treatment of chemotherapy plus bevacizumab were identified. The efficacy data included progression-free survival (PFS), overall survival (OS), and overall response rate (ORR), and the safety data contained the 60-day all-cause mortality rate, adverse events (AEs), and specific toxicity such as hypertension, thrombosis, bleeding, proteinuria, gastrointestinal perforation, diarrhea, and leucopenia. Result  There was a significant PFS benefit (P = 0.00; hazards ratio [HR] = 0.66) and OS benefit (P = 0.00; HR = 0.77) in favor of the combined treatment. The ORR was significantly higher on the bevacizumab-containing arm (P = 0.021; relative risk [RR] = 1.5), while CR was comparable between the two arms (P = 0.09). A higher incidence of grade 3/4 AEs, grade 3/4 hypertension, grade 3/4 thromboembolic/thrombotic events, grade 3/4 bleeding, and gastrointestinal perforation was associated with the bevacizumab group. The two treatment groups were similar in terms of grade 3/4 proteinuria, grade 3/4 leukopenia, grade 3/4 diarrhea, and the 60-day all-cause mortality rate. Conclusion  The addition of bevacizumab to chemotherapy confers a clinically meaningful and statistically significant improvement in OS, PFS, and ORR. Its side effects are predictable and manageable and do not compound the incidence or severity of toxicities from chemotherapy.     

Activated T cells and cytokine-induced CD3+CD56+ killer cells

 Over the past two decades, attempts have been made to develop immunotherapy for patients with cancer. A significant obstacle to the development of successful adoptive immunotherapy has been the availability of appropriate cytotoxic cells. Immunologic effector cells such as lymphokine-activated killer (LAK) cells, activated T cells such as tumor-infiltrating lymphocytes (TILs), and cytokine-induced killer (CIK) cells may be suitable to remove residual tumor cells. Received: 7 October 1996 / Accepted: 13 November 1996     

Five-year long-term outcomes of laparoscopic surgery for colon cancer

AIM:To perform a meta-analysis to answer whether long-term recurrence rates after laparoscopic-assisted surgery are comparable to those reported after open surgery.METHODS:A comprehensive literature search of the MEDLINE database,EMBASE database,and the Cochrane Central Register of Controlled Trials for the years 1991-2010 was performed.Prospective randomized clinical trials(RCTs)were eligible if they included patients with colon cancer treated by laparoscopic surgery vs open surgery and followed for more than five years.RESULTS:Three studies involving 2147 patients reported long-term outcomes based on five-year data and were included in the analysis.The overall mortality was similar in the two groups(24.9%,268/1075 in the laparoscopic group and 26.4%,283/1072 in open group).No significant differences between laparoscopic and open surgery were found in overall mortality during the follow-up period of these studies[OR(fixed) 0.92,95%confidence intervals(95%CI):0.76-1.12,P=0.41].No significant difference in the development of overall recurrence was found in colon cancer patients,when comparing laparoscopic and open surgery [2147 pts,19.3%vs 20.0%;OR(fixed)0.96,95% CI:0.78-1.19,P=0.71].CONCLUSION:This meta-analysis suggests that laparoscopic surgery was as efficacious and safe as open surgery for colon cancer,based on the five-year data of these included RCTs.     

慢性HBV感染者、健康人树突状细胞经HBsAg活化后的免疫效应差异

目的:研究慢性HBV感染者、健康人外周血树突状细胞(dendriticcells,DC)经HBsAg活化后的免疫功能的差异.方法:从慢性HBV感染者、健康人外周血中培养扩增DC和CIK,在DC成熟前加入纯的HBsAg刺激,并再与同一来源的CIK共同培养.用流式细胞仪检测DC、CIK表型,用ELISA法检测DC、CIK共培养上清液中的IL-12浓度,用CCK-8比色法测定DC诱导CIK对HepG2.2.15细胞的杀伤活性.结果:未经HBsAg致敏的健康人DC表面标志CDla、CD80及CD83明显高于慢性HBV感染者(P<0.05);经HBsAg致敏的健康人DC表面标志均高于慢性HBV感染者,差异具有统计学意义(P<0.01);慢性HBV感染者经HBsAg致敏的DC表面标志与未经HBsAg致敏无显著性差异.CIK细胞CD3、CD8、CD3、CD56的双阳性表达率,健康人HBsAg致敏者明显高于慢性HBV感染者及未经HBsAg致敏的健康人(P<0.01,P<0.05);慢性HBV感染组HBsAg致敏与未经HBsAg致敏者比较无显著性差异(P>0.05).HBsAg致敏DC诱导CIK对HepG2.2.15细胞的杀伤率,健康人显著高于慢性HBV感染者(P<0.01).健康人HBsAg致敏DC、CIK共培养上清液中的IL-12浓度显著高于慢性HBV感染者(P<0.001);慢性HBV感染者HBsAg致敏与未经HBsAg致敏IL-12含量差异不显著(P>0.05).结论:慢性HBV感染者、健康人DC经HBsAg活化后对HepG2.2.15细胞的免疫效应存在显著差异:健康人高于慢性HBV感染者.