Ethanol changes Nestin-promoter induced neural stem cells to disturb newborn dendritic spine remodeling in the hippocampus of mice

Adolescent binge drinking leads to long-lasting disorders of the adult central nervous system,particularly aberrant hippocampal neurogenesis.In this study,we applied in vivo fluorescent tracing using NestinCreERT2::Rosa26-tdTomato mice and analyzed the endogenous neurogenesis lineage progression of neural stem cells(NSCs)and dendritic spine formation of newborn neurons in the subgranular zone of the dentate gyrus.We found abnormal orientation of tamoxifen-induced tdTomato+(tdTom^(+))NSCs in adult mice 2 months after treatment with EtOH(5.0 g/kg,i.p.)for 7 consecutive days.EtOH markedly inhibited tdTom^(+)NSCs activation and hippocampal neurogenesis in mouse dentate gyrus from adolescence to adulthood.EtOH(100 mM)also significantly inhibited the proliferation to 39.2%and differentiation of primary NSCs in vitro.Adult mice exposed to EtOH also exhibited marked inhibitions in dendritic spine growth and newborn neuron maturation in the dentate gyrus,which was partially reversed by voluntary running or inhibition of the mammalian target of rapamycinenhancer of zeste homolog 2 pathway.In vivo tracing revealed that EtOH induced abnormal orientation of tdTom+NSCs and spatial misposition defects of newborn neurons,thus causing the disturbance of hippocampal neurogenesis and dendritic spine remodeling in mice.

Relationship between Phenotypic Changes of Dendritic Cell Subsets and the Onset of Plateau Phase during Intermittent Interferon Therapy in Patients with CHB

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86.Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer.Results In total,143 patients were enrolled(NH group,n=49;NA group,n=47;P group,n=47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001.Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

Overall clinical course of indeterminate dendritic cell tumor patients without skin lesions:A rare case report

BACKGROUND Indeterminate dendritic cell tumor(IDCT)is a rare tumor of immune cells,and IDCT patients without skin lesions are rarely reported.Therefore,the clinical course in this type of patient is unclear,and further research on the underlying pathological mechanisms and appropriate treatments is needed.CASE SUMMARY This study describes a female IDCT patient with bile duct lesions.The strong mimicry of IDCT lesions confused doctors,and consequently,this patient,who had no skin lesions,was first diagnosed with cholangiocarcinoma.Then,she presented with persistent abdominal distension without jaundice.Enlarged mesenteric lymph nodes along with massive ascites were observed in the subsequent imaging examination.However,no tumor cells or pathogens were found in the three subsequent ascites analyses.It took 2 years to reach the correct diagnosis,which was eventually obtained by performing surgery for biopsy of the patient’s abdominal lymph nodes.However,by then,she was already in a cachexic state.Finally,she received a cycle of cyclophosphamide therapy and was advised to visit a hospital specializing in rare diseases.CONCLUSION For IDCT patients without skin lesions,early biopsy is the key to obtaining a correct diagnosis.Moreover,the collective management of IDCT patients is important.Further histological and molecular biology studies based on human specimens are critical for understanding the pathological mechanism of dendritic cell tumors in the future.

Azacitidine maintenance therapy for blastic plasmacytoid dendritic cell neoplasm allograft: A case report

BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare,highly invasive malignant neoplasm.There is no universally accepted standard of care because of its rarity and the dearth of prospective research.It is still challenging for some patients to achieve persistent clinical remission or cure,despite the success of allogeneic hematopoietic stem cell transplantation(allo-HSCT),indicating that there is still a significant recurrence rate.We report a case of prevention of BPDCN allograft recurrence by azacitidine maintenance therapy and review the relevant literature.CASE SUMMARY We report a 41-year-old man with BPDCN who was admitted to hospital due to skin sclerosis for>5 mo’duration.BPDCN was diagnosed by combined clinical assessment and laboratory examinations.Following diagnosis,the patients underwent induction consolidation chemotherapy to achieve the first complete remission,followed by bridging allo-HSCT.Post-transplantation,azacitidine(75 mg/m2 for 7 d)was administered as maintenance therapy,with repeat administration every 4–6 wk and appropriate extension of the chemotherapy cycle.After 10 cycles,the patient has been disease free for 26 mo after transplantation.Regular assessments of bone marrow morphology,minimal residual disease,full donor chimerism,Epstein–Barr virus,and cytomegalovirus all yielded normal results with no abnormalities detected.CONCLUSION Azacitidine may be a safe and effective maintenance treatment for BPDCN following transplantation because there were no overt adverse events during the course of treatment.

Blastic plasmacytoid dendritic cell neoplasm in Jinhua,China:Two case reports

BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare and clinically aggressive hematologic malignancy originating from the precursors of plasmacytoid dendritic cells.BPDCN often involves the skin,lymph nodes,and bone marrow,with rapid clinical progression and a poor prognosis.The BPDCN diagnosis is mainly based on the immunophenotype.CASE SUMMARY In this paper,we retrospectively analyzed 2 cases of BPDCN.Both patients were elderly males.The lesions manifested as skin masses.Morphological manifestations included diffuse and dense tumor cell infiltration of the dermis and subcutaneous tissues.Immunohistochemistry staining showed that cluster of differentiation CD4,CD56,CD43,and CD123 were positive.CONCLUSION In this paper,we retrospectively analyzed 2 cases of BPDCN.Both patients were elderly males.The lesions manifested as skin masses.Morphological manifestations included diffuse and dense tumor cell infiltration of the dermis and subcutaneous tissues.Immunohistochemistry staining showed that cluster of differentiation CD4,CD56,CD43,and CD123 were positive.

Study on mechanism of increased allergenicity induced by Ara h 3 from roasted peanut using bone marrow-derived dendritic cells

Little information was so far available about allergenic mechanism of the roasted peanut allergens during initial stages of allergy.The purpose of this study was to determine the influence of roasting(150℃,20 min)on biochemical and biological properties of Ara h 3,a major peanut allergen.Allergenicity of roasted peanut emulsion to mice,differences in uptakes between Ara h 3 purified from raw peanuts(named as Ara h 3-Raw)and that purified from roasted peanuts(named as Ara h 3-Roasted)by bone marrow-derived dendritic cells(BMDCs)and the implication of cell surface receptors involving in uptake,and changes in glycosylation and structure of Ara h 3 after roasting were analyzed in this study.This study suggested that roasting increased allergenicity of peanut to BALB/c mice.Maillard reaction and structural changes of Ara h 3 induced by roasting significantly altered the uptake of Ara h 3-Roasted by BMDCs,and modified Ara h 3 fate in processes involved in immunogenicity and hyper allergenicity,indicating that food processing pattern can change food allergenicity.

Dendritic cells engineered to secrete anti-Dc R3 antibody augment cytotoxic T lymphocyte response against pancreatic cancer in vitro

AIM To investigate the enhanced cytotoxic T lymphocyte responses against pancreatic cancer(PC) in vitro induced by dendritic cells(DCs) engineered to secrete anti-DcR 3 monoclonal antibody(mA b).METHODS DCs, T lymphocytes and primary PC cells were obtained from PC patients. DCs were transfected with a designed humanized anti-Dc R3 monoclonal antibody heavy and light chain m RNA and/or total tumor RNA(DC-tumor-anti-Dc R3 RNA or DC-total tumor RNA) by using electroporation technology. The identification, concentration and function of anti-DcR 3 mA b secreted by DC-tumor-anti-Dc R3 RNA were determined by western blotting and enzyme-linked immunosorbent assay. After co-culturing of autologous isolated PC cells with target DCs, the effects of secreting anti-DcR 3 mA b on RNA-DCs' viability and apoptosis were assessed by MTT assay and flow cytometry. Analysis of enhanced antigen-specific immune response against PC induced by anti-DcR 3 mA b secreting DCs was performed using a 51 Cr releasing test. T cell responses induced by RNAloaded DCs were analyzed by measuring cytokine levels, including IFN-γ, IL-10, IL4, TNF-α and IL-12.RESULTS The anti-Dc R3 m Ab secreted by DCs reacted withrecombinant human Dc R3 protein and generated a band with 35 k Da molecular weight. The secreting m Ab was transient, peaking at 24 h and becoming undetectable after 72 h. After co-incubation with DCtumor-anti-Dc R3 RNA for designated times, the Dc R3 level in the supernatant of autologous PC cells was significantly down-regulated(P < 0.05). DCs secreting anti-Dc R3 m Ab could improve cell viability and slow down the apoptosis of RNA-loaded DCs, compared with DC-total tumor RNA(P < 0.01). The anti-Dc R3 m Ab secreted by DC-tumor-anti-Dc R3 RNA could enhance the induction of cytotoxic T lymphocytes(CTLs) activity toward RNA-transfected DCs, primary tumor cells, and PC cell lines, compared with CTLs stimulated by DC-total tumor RNA or control group(P < 0.05). Meanwhile, the antigen-specific CTL responses were MHC class I-restricted. The CD4+ T cells and CD8+ T cells incubated with anti-DcR 3 mA b secreting DCs could produce extremely higher level IFN-γ and lower level IL4 than those incubated with DC-total tumor RNA or controls(P < 0.01).CONCLUSION DCs engineered to secrete anti-Dc R3 antibody can augment CTL responses against PC in vitro, and the immune-enhancing effects may be partly due to their capability of down-regulating DC apoptosis and adjusting the Th1/Th2 cytokine network.

Flow cytometry assay of myeloid dendritic cells (mDCs)in peripheral blood during acute hepatitis C:Possible pathogenetic mechanisms

瞄准：到驴骨髓的的树枝状的房间(CD11c+) 的表示子集在在感染的自然科学的尖锐 HCV 肝炎和它的可能的参与期间。方法：我们与尖锐丙肝(AHC )( 组 A ) 注册了 11 个病人，有尖锐肝炎 A (啊哈) 的 10 个病人(同样易传染的控制 -- 组 B ) 并且在这的 10 个健康施主(组 C ) 学习。所有病人经历了选择流动血细胞计数 gating 策略估计骨髓的的树枝状的房间(mDCs ) 的外部数字在尖锐肝炎期间理解可能的角色和差别。结果：有尖锐 HCV 肝炎的 11 个病人中的八个没与健康个人相比显示出 mDCs 的任何增加，当 mDCs 的重要减少在绝对房间计数被发现时(z =-2.37；P【0.05 ) 并且百分比(z =-2.30；P【0.05 ) 同样与啊哈相比。相反，留下组 A 的三个病人有是的一个更高的 mDCs 数字和百分比发生在组 B。在六个月以后，有趣地，那些病人没证明 mDCs 子集的任何增加长期地被感染。当三在 HAV 急性感染随外部 mDCs 的增加使遭到，，时，解决了病。结论：mDCs 的增加的缺乏可能在尖锐丙肝期间是涉及感染的 chronicization 的一个重要因素。

Emerging roles of plasmacytoid dendritic cell crosstalk in tumor immunity

Plasmacytoid dendritic cells(pDCs)are a pioneer cell type that produces type I interferon(IFN-I)and promotes antiviral immune responses.However,they are tolerogenic and,when recruited to the tumor microenvironment(TME),play complex roles that have long been a research focus.The interactions between p DCs and other components of the TME,whether direct or indirect,can either promote or hinder tumor development;consequently,p DCs are an intriguing target for therapeutic intervention.This review provides a comprehensive overview of p DC crosstalk in the TME,including crosstalk with various cell types,biochemical factors,and microorganisms.An in-depth understanding of p DC crosstalk in TME should facilitate the development of novel p DC-based therapeutic methods.

Dendritic Cell Algorithm with Bayesian Optimization Hyperband for Signal Fusion

The dendritic cell algorithm(DCA)is an excellent prototype for developing Machine Learning inspired by the function of the powerful natural immune system.Too many parameters increase complexity and lead to plenty of criticism in the signal fusion procedure of DCA.The loss function of DCA is ambiguous due to its complexity.To reduce the uncertainty,several researchers simplified the algorithm program;some introduced gradient descent to optimize parameters;some utilized searching methods to find the optimal parameter combination.However,these studies are either time-consuming or need to be revised in the case of non-convex functions.To overcome the problems,this study models the parameter optimization into a black-box optimization problem without knowing the information about its loss function.This study hybridizes bayesian optimization hyperband(BOHB)with DCA to propose a novel DCA version,BHDCA,for accomplishing parameter optimization in the signal fusion process.The BHDCA utilizes the bayesian optimization(BO)of BOHB to find promising parameter configurations and applies the hyperband of BOHB to allocate the suitable budget for each potential configuration.The experimental results show that the proposed algorithm has significant advantages over the otherDCAexpansion algorithms in terms of signal fusion.

Dendritic Cell Algorithm with Grouping Genetic Algorithm for Input Signal Generation

The artificial immune system,an excellent prototype for developingMachine Learning,is inspired by the function of the powerful natural immune system.As one of the prevalent classifiers,the Dendritic Cell Algorithm(DCA)has been widely used to solve binary problems in the real world.The classification of DCA depends on a data preprocessing procedure to generate input signals,where feature selection and signal categorization are themain work.However,the results of these studies also show that the signal generation of DCA is relatively weak,and all of them utilized a filter strategy to remove unimportant attributes.Ignoring filtered features and applying expertise may not produce an optimal classification result.To overcome these limitations,this study models feature selection and signal categorization into feature grouping problems.This study hybridizes Grouping Genetic Algorithm(GGA)with DCA to propose a novel DCA version,GGA-DCA,for accomplishing feature selection and signal categorization in a search process.The GGA-DCA aims to search for the optimal feature grouping scheme without expertise automatically.In this study,the data coding and operators of GGA are redefined for grouping tasks.The experimental results show that the proposed algorithm has significant advantages over the compared DCA expansion algorithms in terms of signal generation.

Effect of a cancer vaccine prepared by fusions of hepatocarcinoma cells with dendritic cells

AIM To prepare a cancer vaccine (H22-DC) expressing high levels of costimulatory molecules based on fusions of hepatocarcinoma cells ( H22 ) with dendritic cells (DC) of mice and to analyze the biological characteristics and induction of specific CTL activity of H22-DC.``METHODS DCs were isolated from murine spleen by metrizamide density gradient centrifugation, purified based on its characteristics of semi-adhesion to culture plates and FcR , and were cultured in the medium containing GM. CSF and IL-4. A large number of DC were harvested. DCs were then fused with H22 cells by PEG and the fusion cells were marked with CDllc MicroBeads. The H22-DC was sorted with Mimi MACS sorter. The techniques of cell culture, immunocytochemistry and light microscopy were also used to test the characteristice of growth and morphology of H22-DC in vitro. As the immunogen, H22-DC was inoculated subcutaneously into the right armpit of BALB/C mice, and their tumorigenicity in vive was observed. MTT was used to test the CTL activity of murine spleen in vitro.``RESULTS DC cells isolated and generated were CD1 lc +cells with irregular shape, and highly expressed CD80,CD86 and CD54 molecules. H22 cells were CDllc cells with sphericel shape and bigger volume, and did not express CD80, CD86 and CD54 molecules. H22-DC was CDllc+ cells with bigger volume, being spherical, flat or irregular in shape, and highly expressed CD80, CD86 and CD54 molecules, too. H22-DC was able to divide and proliferate in vitro, but its activity of proliferation was significantly decreased as compared with H22 cells and its growth curve was flatter than H22 cells. After subcutaneous inoculation over 60 days, 1-12_2-DC showed no tumorigenecity in mice, which was significantly different from control groups (P＜ 0.01 ) . The spleen CTL activity against H22 cells in mice implanted with fresh H22-DC was significantly higher than control groups (P＜ 0.0l).``CONCLUSION H22-DC could significantly stimulate the specific CTL activity of murine spleen, which suggests that the fusion cells have already obtained the function of antigen presenting of parental DC and could present H22specific antigen which has not been identified yet, and H22-DC could induce antitumor immune response; although simply mixed H22 cells with DC could stimulate the specific CTL activity which could inhibit the growth of tumor in some degree, it could not prevent the generation of tumor. It shows that the DC vaccine is likely to become a helpful approach in immunotherapy of hepstocarcinoma.

Intestinal antigen-presenting cells in mucosal immune homeostasis:Crosstalk between dendritic cells,macrophages and B-cells

The intestinal immune system maintains a delicate balance between immunogenicity against invading pathogens and tolerance of the commensal microbiota.Inflammatory bowel disease(IBD)involves a breakdown in tolerance towards the microbiota.Dendritic cells(DC),macrophages(MΦ)and B-cells are known as professional antigen-presenting cells(APC)due to their specialization in presenting processed antigen to T-cells,and in turn shaping types of T-cell responses generated.Intestinal DC are migratory cells,unique in their ability to generate primary T-cell responses in mesenteric lymph nodes or Peyer’s patches,whilst MΦand B-cells contribute to polarization and differentiation of secondary T-cell responses in the gut lamina propria.The antigen-sampling function of gut DC and MΦenables them to sample bacterial antigens from the gut lumen to determine types of T-cell responses generated.The primary function of intestinal B-cells involves their secretion of large amounts of immunoglobulin A,which in turn contributes to epithelial barrier function and limits immune responses towards to microbiota.Here,we review the role of all three types of APC in intestinal immunity,both in the steady state and in inflammation,and how these cells interact with one another,as well as with the intestinal microenvironment,to shape mucosal immune responses.We describe mechanisms of maintaining intestinal immune tolerance in the steady state but also inappropriate responses of APC to components of the gut microbiota that contribute to pathology in IBD.

Dysfunction of peripheral blood dendritic cells from patients with chronic hepatitis B virus infection

AIM To identify the property of dendritic cella (DCs) of peripheral blood monocytes (PBMC) in patlents with chronic HBV infection.METHODS Twenty patients with persistent HBV infectlon were included in this study, 10 healthy subjects being used as a control group. The peripheral blood mononuclear cells (PBMC) of T cell-depleted populations were incubated and induced into mature dendritic cells in the RPMI-1640 medium in the presence of cytokines GMCSF, IL-4, FLt-3, TNF-α and 100 mL@ L-1 of fetal calf serum for a total of 10 - 12 days. The expressions of surface markers on DCs were evaluated using flow cytometric analysis. ELISA method was used to determine the cytokine levels of interleukin-12 (IL-12) and IL-10 in the supernatant produced by DCs. For detection of the stimulatory capacity of DCs to T cell proliferation,mytomycin C-treated DC were incubated with allogenic T cells.RESULTS A typical morphology of mature DCs from healthy subjects and HBV-infected patients was induced in in vitro incubation, but the proliferation ability and cellular number of DCs from HBV-infected patients significantly decreased compared with healthy individuals. In particular, the expression levels of HLADR, CD80 (B7-1) and CD86 (B7-2) on DC surface from patients were also lower than that from healthy individuals (0.46 vs 0.92 for HLA-DR, 0.44 vs 0.88 for CD80 and 0.44 vs 0. 84 for CD86, P＜ 0.05). The stimulatory capacity and production of IL-12 of DCs from patients in allogenic mixed lymphocyte reaction (AMLR) significantly decreased, but the production level of nitric oxide (NO) by DCa simultaneously increased compared with healthy subjects (86± 15 vs 170±22 μmoI@L 1, P＜0.05).CONCLUSION The patients with chronic HBV infection have the defective function and immature phenotype of dendritic cells, which may be associated with the inability of efficient presentation of HBV antigens to host immune system for the clearance of HBV.

Probiotic Bio-Three induces Th1 and anti-inflammatory effects in PBMC and dendritic cells

AIM:To investigate the immune response of peripheral blood mononuclear cells(PBMCs)and dendritic cells (DCs)that were stimulated by probiotic preparations. METHODS:PBMCs were isolated,cultured,and stimulated with Bio-Three(a mixture of Bacillus mesentericus, Clostridium butyricum and Enterococcus faecalis;105, 10 6 and 10 7 CFU/mL for 24 h).Cytokine production of (1)circulating PBMCs;(2)PBMCs stimulated by probiotic preparation;(3)monocyte-derived DCs;and(4)DC andT cell co-culture was determined by enzyme-linked immunosorbent assay.Phenotypic analysis of circulating PBMCs was also investigated by flow cytometry.Blood was obtained from individuals who consumed Bio-Three (10 9 CFU/d B.mesentericus,C.butyricum and E.faecalis) for 2 wk,or those who did not take probiotics orally. RESULTS:In culture supernatants,interferon-γ(IFN-γ) and interleukin(IL)-10 production increased,but IL-4 and tumor necrosis factor-α(TNF-α)production by PBMCs decreased after 1 and 2 wk of probiotic treatment.Flow cytometry was also performed on day 14 and detected enhanced expression of CD11b,HLA-DR, CD4,CD45RA,CD25,CD44 and CD69 in response to Bio-Three.Furthermore,IL-10 and IL-12 were upregulated in supernatants of monocyte-derived DCs,and IFN-γand IL-10 were enhanced in supernatants of CD4 + T cells co-cultured with DCs. CONCLUSION:Bio-Three appeared to stimulate the Th1 immune response,downregulate pro-inflammatory cytokines(TNF-α)and upregulate anti-inflammatory cytokine(IL-10).Probiotics could be effective in activation of PBMCs and DCs.

Clostridium butyricum alleviates intestinal low-grade inflammation in TNBS-induced irritable bowel syndrome in mice by regulating functional status of lamina propria dendritic cells

BACKGROUND Irritable bowel syndrome (IBS) is one of the most common functional gastroenterological diseases characterized by abnormal visceral sensitivity and lowgrade inflammation. The role of Clostridium butyricum (C. butyricum) in reducing intestinal low-grade inflammation via immune pathways has been well defined. However, the detailed mechanisms of the effects of C. butyricum on intestinal mucosal immunity, especially on immune cells of the lamina propria, remain unclear. Dendritic cells (DCs), which are important immune cells, secrete proinflammatory cytokines (IL-1β, IL-6, and others) and express T cell immunoglobulin and mucin domain-3 (TIM3), promoting proliferation and activation of DCs, and mediating Th1 and Th17 inflammatory responses. AIM To investigate the role of DCs in the development of IBS in a rat model and to understand the regulation of DCs after C. butyricum intervention. METHODS An IBS animal model was established using C57BL/6 mice, and C. butyricum was continuously administered via the intragastric route to simulate different intestinal immune states. Intestinal visceral hypersensitivity and histopathology were assessed using the abdominal withdrawal reflex (AWR) test and hematoxylin & eosin (H&E) staining, respectively. The expression of proinflammatory cytokines (IL-1β and IL-6) and TIM3 was analyzed by Western blot analysis and real-time PCR. Flow cytometry was applied to analyze the quantity, function, and membrane molecule TIM3 of the lamina propria dendritic cells (LPDCs). The regulatory effect of C. butyricum was verified in bone marrowderived dendritic cells by in vitro experiments. RESULTS The secretion of proinflammatory cytokines (IL-1β and IL-6) in mice with IBS was significantly increased compared with that of the control group, which suggested that the intestinal mucosa in mice with IBS was in a low-grade inflammatory state. The expression of CD11C+CD80+ and CD11c+TIM3+ in intestinal LPDCs in mice with IBS increased significantly. Meanwhile, the cytokines (IL-1β and IL-6) were significantly reduced after the intervention with probiotic C. butyricum. The amount and function of LPDCs and the TIM3 on the surface of the LPDCs were decreased with the alleviation of the intestinal inflammatory response. CONCLUSION The results suggest that C. butyricum regulates the amount and functional status of LPDCs in the intestinal mucosa of mice with IBS, and therefore modulates the local immune response in the intestine.

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.

Influence of granulocyte-macrophage colonystimulating factor and tumor necrosis factor on anti-hepatoma activities of human dendritic cells

INTRODUCTIONDendritic cells (DCs) play a key regulatory role inantitumor immunity,especially in its immuneaccessory role via MHC-Ⅰ molecules.We haverecently reported that DCs were able to enhance thekilling activity of Lymphokine and PHA activatedkiller (LPAK) cells in vitro.In the presentstudy,we evaluated the effects of GM-CSF andTNF upon antitumor activities of freshly

Relationship between the Changes of VEGF Level and Dendritic Cells in Peripheral Blood of Patients with Hepatocellular Carcinoma after Transcatheter Arterial Chemoembolization

In order to investigate the relationship between the VEGF level and the counts of dendritic cells （DCs） in peripheral blood of patients with hepatocellular carcinoma （HCC） before and after transcatheter arterial chemoembolization （TACE）, the peripheral blood was obtained from 37 patients with HCC who treated by TACE. The blood was obtained on the day before TACE, the first day, the 7th day and the 15th day after TACE respectively. The counts of DCs were quantified by flow cytometry. The plasma VEGF level was measured by ELESA kit. It was shown after TACE, the counts of DCs in peripheral blood were decreased significantly （P〈0.05）, and the VEGF level in peripheral blood was increased significantly （P〈0.05）. The counts of DCs in peripheral blood had an inverse correlation with the plasma VEGF level （r=-0.57, P〈0.05） after TACE. It was concluded that in patients with HCC after TACE, the increased plasma VEGF level appeared to have the effect to suppress the maturation of DCs, which may contribute to reduction of the body＇s anti-tumor immunity effect, with a consequence of recur and metastasis of tumor.

Hepatocellular carcinoma-specific immunotherapy with synthesized α1,3-galactosyl epitope-pulsed dendritic cells and cytokine-induced killer cells

AIM: To evaluate the safety and clinical efficacy of a new immunotherapy using both α-Gal epitope-pulsed dendritic cells (DCs) and cytokine-induced killer cells.METHODS: Freshly collected hepatocellular carcinoma(HCC) tumor tissues were incubated with a mixture of neuraminidase and recombinant α1,3-galactosyltransferase (α1,3GT) to synthesize α-Gal epitopes on carbohydrate chains of the glycoproteins of tumor membranes. The subsequent incubation of the processed membranes in the presence of human natural anti-Gal IgG resulted in the effective phagocytosis to the tumor membrane by DCs. Eighteen patients aged 38-78 years with stage Ⅲ primary HCC were randomLy chosen for the study; 9 patients served as controls, and 9 patients were enrolled in the study group.RESULTS: The evaluation demonstrated that the procedure was safe; no serious side effects or autoimmune diseases were observed. The therapy significantly prolonged the survival of treated patients as compared with the controls (17.1 ± 2.01 mo vs 10.1 ± 4.5 mo,P = 0.00121). After treatment, all patients in the study group had positive delayed hyper sensitivity and robust systemic cytotoxicity in response to tumor lysate as measured by interferon-γ-expression in peripheral blood mononuclear cells using enzyme-linked immunosorbent spot assay. They also displayed increased numbers of CD8-, CD45RO-and CD56-positive cells in the peripheral blood and decreased α-fetoprotein level in the serum.CONCLUSION: This new tumor-specific immunotherapy is safe, effective and has a great potential for the treatment of tumors.