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.

Advancing the understanding and management of blastic plasmacytoid dendritic cell neoplasm:Insights from recent case studies

We specifically discuss the mechanisms of the pathogenesis,diagnosis,and management of blastic plasmacytoid dendritic cell neoplasm(BPDCN),a rare but aggressive haematologic malignancy characterized by frequent skin manifestations and systemic dissemination.The article enriches our understanding of BPDCN through detailed case reports showing the clinical,immunophenotypic,and histopathological features that are critical for diagnosing this disease.These cases highlight the essential role of pathologists in employing advanced immunophenotyping techniques to accurately identify the disease early in its course and guide treatment decisions.Furthermore,we explore the implications of these findings for management strategies,emphasizing the use of targeted therapies such as tagraxofusp and the potential of allogeneic haematopoietic stem cell transplantation in achieving remission.The editorial underscores the importance of interdisciplinary approaches in managing BPDCN,pointing towards a future where precision medicine could significantly improve patient outcomes.

Blastic plasmacytoid dendritic cell neoplasm:Two case reports

BACKGROUND Blastic plasmacytoid dendritic cell tumor(BPDCN)is a rare and highly invasive lymphohematopoietic tumor that originates from plasmacytoid dendritic cells.BPDCN has an extremely poor prognosis.Skin lesions are usually the first manifestation of BPDCN,although the tumor may also invade the bone marrow,lymph nodes,peripheral blood,and other parts of the body,leading to several other manifestations,requiring further differentiation through skin biopsy and immunohistochemistry.CASE SUMMARY In the present paper,the cases of 2 patients diagnosed with BPDCN are discussed.The immunohistochemistry analysis of these 2 patients revealed positivity for CD4,CD56,and CD123.Currently,no standard chemotherapy regimen is available for BPDCN.Therefore,intensive therapy for acute lymphoblastic leukemia was applied as the treatment method for these 2 cases.CONCLUSION Although allogeneic bone marrow transplantation could be further effective in prolonging the median survival the ultimate prognosis was unfavorable.Future treatment modalities tailored for elderly patients will help prolong survival.

3D Collagen Gels:A Promising Platform for Dendritic Cell Culture in Biomaterials Research

The three-dimensional(3D)cell culture system has garnered significant attention in recent years as a means of studying cell behavior and tissue development,as opposed to traditional two-dimensional cultures.These systems can induce specific cell reactions,promote specific tissue functions,and serve as valuable tools for research in tissue engineering,regenerative medicine,and drug discovery.This paper discusses current developments in the field of three-dimensional cell culture and the potential applications of 3D type 1 collagen gels to enhance the growth and maturation of dendritic cells.

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.

Changes of the Transcriptional Levels of Molecules Associated with Endogenous Antigen Processing and Presentation in Porcine Skin-derived Dendritic Cells Infected with PCV2 in vivo

[Objective] This study aimed to investigate the changes of the transcriptional levels of molecules associated with endogenous antigen processing and presenta- tion in porcine skin-derived dendritic cells infected with PCV2 in vivo. [Method] Healthy 40-day-old Landrace piglets were infected with porcine circovirus type 2 （PCV2） and euthanized on the 34, 7rd, 14th, 21st and 35th d post inoculation （DPI）. The porcine skin-derived dendritic cells （DCs） were collected to analyze the transcrip- tional levels of molecules （LMP7, UBP, MHC-I, calreticulin） associated with endogenous antigen processing and presentation by using real-time fluorescent quantitative PCR （real-time FQ-PCR）. [Result] The results showed that the level of LMP7 mR- NAs was reduced significantly on the 3DPI （P〈0.05）; the level of UBP mRNAs was consistently up-regulated, which increased significantly on the 21DPI and 35DPI （P〈 0.05）; the level of MHC-I mRNAs was significantly down-regulated on the 7DPI （P〈 0.05）; the level of calreticulin mRNAs was up-regulated slightly without significant dif- ference. [Conclusion] PCV2 can inhibit the endogenous antigen processing and presentation ability of porcine skin-derived DCs at early stages of infection.

Culture of Porcine Peripheral Blood Monocyte-derived Dendritic Cells in vitro

[Objective] This study aimed to establish an in vitro culture model for porcine peripheral blood monocyte-derived dendritic cells （MoDCs）. [Method] Fresh peripheral blood mononuclear cells （PBMCs） were separated from pig, and precursor dendritic cells were obtained by adherence method. The dendritic cells were treated by recombinant porcine granulocyte-monocyte colony stimulating factor （rpGM-CSF） and recombinant porcine interleukin-4 （rplL-4） together, and lipopolysaccharide （LPS） respectively. The cells in different time periods were collected. The morphology of the collected cells was observed by scanning electron microscopy; the expression of surface molecules and phagocytic ability to FITC-dextran were detected by flow cy- tometry; and the stimulating ability for allogeneic T cells was detected by mixed lymphocyte reaction. [Result] The DCs suffering maturation induction in vitro showed typical dendritic morphology; compared with those of DCs untreated by LPS, the cell surface expression of CDla, CD80, CD86, SLAII and CD172a of DCs treated by LPS was significantly increased, the phagocytic ability was reduced slightly, and the stimulating ability for allogeneic T cells was enhanced to some extent. [Conclusion] An in vitro culture method was successfully established for porcine MoDCs in this study, laying a foundation for further study on the role of porcine MoDCs in immunoregulation and anti-virus infection.

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.

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

AIM: To identify the property of dendritic cells (DCs) of peripheral blood monocytes (PBMC) in patients with chronic HBV infection. METHODS: Twenty patients with persistent HBV infection 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 GM-CSF, IL-4, FLt-3,TNF-alpha and 100mL.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 HLA-DR, 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 DCs simultaneously increased compared with healthy subjects (86 +/- 15 vs 170 +/- 22 micromol.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.

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 (M&#x003a6;) 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&#x02019;s patches, whilst M&#x003a6; and 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 M&#x003a6; enables 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.

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.

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.

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

AIM: To prepare a cancer vaccine (H(22)-DC) expressing high levels of costimulatory molecules based on fusions of hepatocarcinoma cells (H(22)) with dendritic cells (DC) of mice and to analyze the biological characteristics and induction of specific CTL activity of H(22)-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 H(22) cells by PEG and the fusion cells were marked with CD11c MicroBeads. The H(22)-DC was sorted with Mimi MACS sorter. The techniques of cell culture, immunocytochemistry and light microscopy were also used to test the characteristics of growth and morphology of H(22)-DC in vitro. As the immunogen, H(22)-DC was inoculated subcutaneously into the right armpit of BALB/C mice, and their tumorigenicity in vivo was observed. MTT was used to test the CTL activity of murine spleen in vivo. RESULTS: DC cells isolated and generated were CD11c+ cells with irregular shape, and highly expressed CD80, CD86 and CD54 molecules. H22 cells were CD11c- cells with spherical shape and bigger volume, and did not express CD80, CD86 and CD54 molecules.H(22)-DC was CD11c+ cells with bigger volume, being spherical, flat or irregular in shape, and highly expressed CD80, CD86 and CD54 molecules, too. H(22)-DC was able to divide and proliferate in vitro, but its activity of proliferation was significantly decreased as compared with H(22) cells and its growth curve was flatter than H(22) cells. After subcutaneous inoculation over 60 days, H(22)-DC showed no tumorigenecity in mice, which was significantly different from control groups (P【0.01). The spleen CTL activity against H(22) cells in mice implanted with fresh H(22)-DC was significantly higher than control groups (P 【 0.01). CONCLUSION: H(22)-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 H(22)specific antigen which has not been identified yet, and H(22)-DC could induce antitumor immune response; although simply mixed H(22) 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 hepatocarcinoma.

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.