Tumor-derived DEFB1 induces immune tolerance by inhibiting maturation of dendritic cell and impairing CD8+T cell function in esophageal squamous cell carcinoma

Objective:CD8+T cells are the key effector cells in the anti-tumor immune response.The mechanism underlying the infiltration of CD8+T cells in esophageal squamous cell carcinoma(ESCC)has not been clearly elucidated.Methods:Fresh ESCC tissues were collected and grouped according to the infiltration density of CD8+T cells.After the transcriptome sequencing on these samples and the combined analyses with The Cancer Genome Atlas(TCGA)ESCC data,a secreted protein DEFB1 was selected to explore its potential role in the infiltration of CD8+T cells.Bioinformatics analyses,histological verification and in vitro experiments were then performed.Results:DEFB1 was highly expressed in ESCC,and the high expression of DEFB1 was an independent risk factor for overall survival.Since the up-regulation or down-regulation of DEFB1 did not affect the proliferation,migration and apoptosis of ESCC cells,we speculated that the oncogenic effect of DEFB1 was achieved by regulating microenvironmental characteristics.Bioinformatics analyses suggested that DEFB1 might play a major role in the inflammatory response and anti-tumor immune response,and correlate to the infiltration of immature dendritic cell(imDC)in ESCC.Histological analyses further confirmed that there were less CD8+T cells infiltrated,less CD83+mature DC(mDC)infiltrated and more CD1a+imDC infiltrated in those ESCC samples with high expression of DEFB1.After the treatment with recombinant DEFB1 protein,the maturation of DC was hindered significantly,followed by the impairment of the killing effects of T cells in both 2D and 3D culture in vitro.Conclusions:Tumor-derived DEFB1 can inhibit the maturation of DC and weaken the function of CD8+T cells,accounting for the immune tolerance in ESCC.The role of DEFB1 in ESCC deserves further exploration.

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.

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.

Cilostazol inhibits plasmacytoid dendritic cell activation and antigen presentation

Background Cilostazol, an anti-platelet drug for treating coronary heart disease, has been reported to modulate immune cell functions Plasmacytoid dendritic cells （pDCs） have been found to participate in the progression of atherosclerosis mainly through interferon ct （IFN-ct） production. Whether cilostazol influences pDCs activation is still not clear. In this study, we aimed to investigate the effects of cilostazol on cell activation and antigen presentation ofpDCs in vitro in this study. Methods Peripheral blood mononuclear cells isolated by Ficoll cen- trifugation and pDCs sorted by flow cytometry were used in this study. After pretreated with cilostazol for 2 h, cells were stimulated with CpG-A, R848 or virus for 6 h or 20 h, or stimulated with CpG-B for 48 h and then co-cultured with naive T cell for five days. Cytokines in supernatant and intracellular cytokines were analyzed by ELISA or flow cytometry respectively. Results Our data indicated that cilostazol could inhibit IFN-α and tumor necrosis factor α （TNF-α） production from pDCs in a dose-dependent manner. In addition, the ability of priming na ve T cells of pDCs was also impaired by cilostazol. The inhibitory effect was not due to cell killing since the viability of pDCs did not change upon cilostazol treatment. Conclusion Cilostazol inhibits pDCs cell activation and antigen presentation in vitro, which may explain how cilostazol protects against atherosclerosis.

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 MΦ 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 MΦ 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.

Heat-shocked tumor cell lysate-pulsed dendritic cells induce effective anti-tumor immune response in vivo

AIM. To study whether heat-shocked tumor cells could enhance the effect of tumor cell lysate-pulsed dendritic cells （DCs） in evoking anti-tumor immune response in vivo. METHODS： Mouse undifferentiated colon cancer cells （CT-26） were heated at 42℃ for 1 h and then frozenthawed. The bone marrow-derived DCs pulsed with heatshocked CT-26 cell lysate （HSCT-26 DCs） were recruited to immunize syngeneic naive BALB/c mice. The cytotoxic activity of tumor specific cytotoxic T lymphocytes （CTLs） in mouse spleen was evaluated by IFN-enzyme-linked immunospot （ELISpot） and LDH release assay. The immunoprophylactic effects induced by HSCT-26 DCs in mouse colon cancer model were compared to those induced by single CT-26 cell lysate-pulsed DCs （CT-26 DCs） on tumor volume, peritoneal metastasis and survival time of the mice. RESULTS： Heat-treated CT-26 cells showed a higher hsp70 protein expression. Heat-shocked CT-26 cell lysate pulsing elevated the co-stimulatory and MHC-Ⅱ molecule expression of bone marrow-derived DCs as well as interleukin-12 p70 secretion. The IFN-y secreting CTLs induced by HSCT-26 DCs were significantly more than those induced by CT-26 DCs （P=0.002）. The former CTLs＇ specific cytotoxic activity was higher than the latter CTLs＇ at a serial E/T ratio of 10：1, 20：1, and 40：1. Mouse colon cancer model showed that the tumor volume of HSCT-26 DC vaccination group was smaller than that of CT-26 DC vaccination group on tumor volume though there was no statistical difference between them （24 mm^3 vs 8 mm^3, P=0.480）. The median survival time of mice immunized with HSCT-26 DCs was longer than that of those immunized with CT-26 DCs （57 d vs 43 d, P = 0.0384）. CONCLUSION： Heat-shocked tumor cell lysate-pulsed DCs can evoke anti-tumor immune response in vivo effectively and serve as a novel DC-based tumor vaccine.

Enhancing Antitumor by Immunization with Fusion of Dendritic Cells and Engineered Tumor Cells

A novel approach for a dentritic cells (DCs) based tumor vaccine was developed for the formation of hybrid engineered J558 after fusion with DCs. To make the hybrid tumor vaccine generate more efficient specific CTL cytotoxicity against wild type tumor cells, we genetically engineered tumor cells with mIL 12 gene prior to the cell fusion. mIL 12 was detected at 870±60 pg/(10 5 cells/ml) in the culture supernatants and the fusion ratio was about 30 % by the co focal microscopic analysis. Vaccination of mice with DCs fused with engineered J558 induced more efficient tumor specific CTL cytotoxicity against wild type tumor cells in vitro and with efficient antitumor immunity in vivo . These results suggest that this approach of using DCs fused with engineered tumor cells could be applied in clinical settings of DCs based cancer vaccines.

Impact of nanoparticles on immune cells and their potential applications in cancer immunotherapy

Nanoparticles represent a heterogeneous collection of materials,whether natural or synthetic,with dimensions aligning in the nanoscale.Because of their intense manifestation with the immune system,they can be harvested for numerous bio-medical and biotechnological advancements mainly in cancer treatment.This review article aims to scrutinize various types of nanoparticles that interact differently with immune cells like macrophages,dendritic cells,T lymphocytes,and natural killer(NK)cells.It also underscores the importance of knowing how nanoparticles influence immune cell functions,such as the production of cytokines and the presentation of antigens which are crucial for effective cancer immunotherapy.Hence overviews of bio-molecular mechanisms are provided.Nanoparticles can improve antigen presentation,boost T-cell responses,and overcome the immunosuppressive tumor environment.The regulatory mechanisms,signaling pathways,and nanoparticle characteristics are also presented for a comprehensive understanding.We review the nanotechnology platform options and challenges in nanoparticlesbased immunotherapy,from an immunotherapy perspective including precise targeting,immune modulation,and potential toxicity,as well as personalized approaches based on individual patient and tumor characteristics.The development of emerging multifunctional nanoparticles and theranostic nanoparticles will provide new solutions for the precision and efficiency of cancer therapies in next-generation practice.

Immunity of Unloaded Dendritic Cells in Lung Melanoma of Mice

In order to investigate the immunity of unloaded dendritic cells （DCs） derived from murine bone marrow to preexisting lung melanoma metastases of mice, MO5 were intravenously injected to induce lung metastases in syngeneic C57BI-/6 mice. Unloaded GM-CSF DCs, PBS and DCs＋SIINFEKEL were subcutaneously injected into the mice, which were divided as experimental group, negative control group and positive control group respectively. Monoclonal antibody was used to deplete NK or T cells separately. The immunity-inhibitory effects on the lung melanoma were observed and the corresponding effector cells were examined. It was found that in the experimental and positive groups, the regression was induced in metastatic nodules in the lungs of tumor-bearing mice, but abrogated by treatment with anti-asialo-GM1 but not anti-CD8. It was concluded that the unloaded DCs could suppress the lung melanoma metastases to some extent, which was mediated by NK cells, and could be used as a potent therapeutic agents for lung tumor.

Dendritic cell subsets in cancer immunity and tumor antigen sensing

Dendritic cells(DCs)exhibit a specialized antigen-presenting function and play crucial roles in both innate and adaptive immune responses.Due to their ability to cross-present tumor cell-associated antigens to naïve T cells,DCs are instrumental in the generation of specific T-cell-mediated antitumor effector responses in the control of tumor growth and tumor cell dissemination.Within an immunosuppressive tumor microenvironment,DC antitumor functions can,however,be severely impaired.In this review,we focus on the mechanisms of DC capture and activation by tumor cell antigens and the role of the tumor microenvironment in shaping DC functions,taking advantage of recent studies showing the phenotype acquisition,transcriptional state and functional programs revealed by scRNA-seq analysis.The therapeutic potential of DC-mediated tumor antigen sensing in priming antitumor immunity is also discussed.

HBsAg loading on dendritic cells in patients with chronic hepatitis B: expressions of phenotypic molecules

BACKGROUND: The antigen reducing ability of dentritic cells (DCs), a kind of antigen presenting cells (APCs) initiating immune response, is associated with the specific immune tolerance of chronic hepatitis B(CHB) patients. However, the dysfunction of DCs can be possibly reversed by the stimulation of antigen peptides. In this study, DCs were cultured from peripheral blood monocytes (PBMCs) in patients with CHB in vitro, and the expression of phenotypic molecules on DCs loaded by different concentrations of HBsAg was observed. METHODS: Forty patients with CHB were divided randomly into 4 groups(10 patients in each group). PBMCs were isolated, and DCs were cultured after addition of granulocyte/macrophage colony-stimulating factor (GMCSF) and interleukin 4(IL-4). On the 9th day, DCs of the experimental groups were loaded at HBsAg concentrations of 2.5mg/L, 5mg/L and 10mg/L for 24 hours, whereas those of the control group were not loaded. An electron microscope was used to analyze the morphological changes of the DCs. The expression of phenotypic molecules on DCs in different groups was detected with flow cytometry. RESULTS: A combination of GM-CSF and IL-4 produced DCs from PBMCs in patients with CHB after being cultured for 9 days, whose morphological changes were tested by an electron microscope. The expression of phenotypic molecules on DCs in the control group was as low as CD83 (8.02±3.99)%, CD80(8.77±2.06)%, and MHC-DR (14.05±2.66)%. Loaded by different concentrations of HBsAg, the up-regulation of phenotypic molecules on DCs was found, with CD83(18.35±2.93)%, CD80(42.63±7.15)% and MHC-DR(47.49±6.59)% in 2.5mg/L HBsAg loading group, CD83(17.88±3.12)%, CD80(45.24± 10.93)% and MHC-DR(47.07±8.52)% in 5mg/L HBsAg loading group and CD83(16.74±2.86)%, CD80(44.59±6.99)% and MHC-DR(48.59±7.42)% in 10mg/L HBsAg loading group, respectively. Compared with the control group, the phenotypic molecules in the experimental groups were all different significantly (P<0.01), but among them, there were no differences (P>0.05). CONCLUSIONS: DCs cultured from PBMCs in the patients with CHB under the conditions of GM-CSF and IL-4 present on the typical dendritic morphology but are immature for expressing low phenotypic molecules. Loaded by different concentrations of HBsAg, the immature DCs can differentiate to mature DCs for expressing increasing phenotypic molecules.

Cinnamon extract suppresses experimental colitis through modulation of antigen-presenting cells

AIM:To investigate the anti-inflammatory effects of cinnamon extract and elucidate its mechanisms for targeting the function of antigen presenting cells.METHODS:Cinnamon extract was used to treat murine macrophage cell line(Raw 264.7),mouse primary antigen-presenting cells(APCs,MHCII+) and CD11c+dendritic cells to analyze the effects of cinnamon extract on APC function.The mechanisms of action of cinnamon extract on APCs were investigated by analyzing cytokine production,and expression of MHC antigens and co-stimulatory molecules by quantitative real-time PCR and flow cytometry.In addition,the effect of cinnamon extract on antigen presentation capacity and APC-dependent T-cell differentiation were analyzed by [H3]-thymidine incorporation and cytokine analysis,respectively.To confirm the anti-inflammatory effects of cinnamon extract in vivo,cinnamon or PBS was orally administered to mice for 20 d followed by induction of experimental colitis with 2,4,6 trinitrobenzenesulfonic acid.The protective effects of cinnamon extract against experimental colitis were measured by checking clinical symptoms,histological analysis and cytokine expression prof iles in inflamed tissue.RESULTS:Treatment with cinnamon extract inhibited maturation of MHCII+ APCs or CD11c+ dendritic cells(DCs) by suppressing expression of co-stimulatory molecules(B7.1,B7.2,ICOS-L),MHCII and cyclooxygenase(COX)-2.Cinnamon extract induced regulatory DCs(rDCs) that produce low levels of pro-inflammatory cytokines [interleukin(IL)-1β,IL-6,IL-12,interferon(IFN)-γ and tumor necrosis factor(TNF)-α] while expressing high levels of immunoregulatory cytokines(IL-10 and transforming growth factor-β).In addition,rDCs generated by cinnamon extract inhibited APC-dependent T-cell proliferation,and converted CD4+ T cells into IL-10high CD4+ T cells.Furthermore,oral administration of cinnamon extract inhibited development and progression of intestinal colitis by inhibiting expression of COX-2 and pro-inflammatory cytokines(IL-1β,IFN-γ and TNF-α),while enhancing IL-10 levels.CONCLUSION:Our study suggests the potential of cinnamon extract as an anti-inflammatory agent by targeting the generation of regulatory APCs and IL-10+ regulatory T cells.

Impact of PRRSV on activation and viability of antigen presenting cells

Porcine reproductive and respiratory syndrome(PRRS) is one of the most important diseases of swine industry. The causal agent, PRRS-virus(PRRSV), is able to evade the host immune response and survive in the organism causing transient infections. Despite all scientific efforts, there are still some gaps in the knowledge of the pathogenesis of this disease. Antigen presenting cells(APCs), as initiators of the immune response, are located in the first line of defense against microorganisms, and are responsible for antigen recognition, processing and presentation. Dendritic cells(DCs) are the main type of APC involved in antigen presentation and they are susceptible to PRRSV infection. Thus, PRRSV replication in DCs may trigger off different mechanisms to impair the onset of a host effective immune response against the virus. On the one side, PRRSV may impair the basic functions of DCs by regulating the expression of major histocompatibility complex class Ⅱ and CD80/86. Other strategy followed by the virus is the induction of cell death of APCs by apoptosis, necrosis or both of them. The impairment and/or cell death ofAPCs could lead to a failure in the onset of an efficient immune response, as long as cells could not properly activate T cells. Future aspects to take into account are also discussed in this review.

Hepatocellular carcinoma-specific immunotherapy with synthesized α1,3-galactosyl epitope-ulsed 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 αl,3-galactosyltrans- ferase （αI,3GT） to synthesize α-Gal epitopes on car- bohydrate chains of the glycoproteins of tumor mem- branes. 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 111 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 pro- cedure was safe; no serious side effects or autoimmune diseases were observed. The therapy significantly pro- longed 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 hypersensitivity and robust systemic cytotoxicity in response to tumor lysate as measured by interferon-y-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 se- rum. CONCLUSION： This new tumor-specific immunotherapy is safe, effective and has a great potential for the treat- ment of tumors.

Inducible expression of endomorphins in murine dendritic cells

Bone marrow precursor cells were extracted from C57BL/6J mice aged 7-8 weeks, and dendritic cells were purified using anti-CD1 lc （a specific marker for dendritic cells） antibody-coated magnetic beads. Immunofluorescence staining revealed that the expression levels of endomorphin-1 and endomorphin-2 were upregulated in dendritic cells activated by lipopolysaccharide. An enzyme Jmmunoassay showed that lipopolysaccharide and other Toll-like receptor ligands promoted the secretion of endomorphin-1 and endomorphin-2 from activated dendritic cells. [3H]-thymidine incorporation demonstrated that endomorphin-1 and endomorphin-2 both inhibited the proliferation of T lymphocyte induced by activated dendritic cells. Furthermore, this immunosuppressive effect was blocked by CTOP, a specific antagonist of IJ-opioid receptors. Our experimental findings indicate that activated dendritic cells can induce the expression and secretion of endomorphins, and that endomorphins suppress T lymphocyte proliferation through activation of iJ-opioid receptors.

An antigen self-assembled and dendritic cell-targeted nanovaccine for enhanced immunity against cancer

The rise of nanotechnology has opened new horizons for cancer immunotherapy.However,most nano vaccines fabricated with nanomaterials suffer from carrier-related concerns,including low drug loading capacity,unpredictable metabolism,and potential systemic toxicity,which bring obstacles for their clinical translation.Herein,we developed an antigen self-assembled nanovaccine,which was resulted from a simple acryloyl modification of the antigen to induce self-assembly.Furthermore,a dendritic cell targeting head mannose monomer and a mevalonate pathway inhibitor zoledronic acid(Zol)were integrated or absorbed onto the nanoparticles(denoted as MEAO-Z)to intensify the immune response.The synthesized nano vaccine with a diameter of around 70 nm showed successful lymph node transportation,high dendritic cell internalization,promoted costimulatory molecule expression,and preferable antigen cross-presentation.In virtue of the above superiorities,MEAO-Z induced remarkably higher titers of serum antibody,stronger cytotoxic T lymphocyte immune responses and IFN-γsecretion than free antigen and adjuvants.In vivo,MEAO-Z significantly suppressed EG7-OVA tumor groth and prolonged the survival time of tumor-bearing mice.These results indicated the translation promise of our self-assembled nano vaccine for immune potentiation and cancer immunotherapy.

Immunotherapy for advanced or recurrent hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is associated with high morbidity and mortality,and is prone to intra-and extrahepatic metastasis due to the anatomical and functional characteristics of the liver.Due to the complexity and high relapse rate associated with radical surgery or radiofrequency ablation,immune checkpoint inhibitors(ICIs)are increasingly being used to treat HCC.Several immunotherapeutic agents,along with their combinations,have been clinically approved to treat advanced or recurrent HCC.This review discusses the leading ICIs in practice and those currently undergoing randomized phase 1-3 trials as monotherapy or combination therapy.Furthermore,we summarize the rapidly developing alternative strategies such as chimeric antigen receptor-engineered T cell therapy and tumor vaccines.Combination therapy is a promising potential treatment option.These immunotherapies are also summarized in this review,which provides insights into the advantages,limitations,and novel angles for future research in establishing viable and alternative therapies against HCC.

Effects of dendritic cell vaccines on hematogenous micrometastasis of bladder cancer carrying for PBL-SCID mice

Objective： To study the effect of dendritic cells loaded with whole tumor antigen on hematogenous micrometastasis of bladder cancer model in hu-PBL-SCID mice. Methods： T24-3 ceil subset was selected from human bladder transitional cell carcinoma T24 cell line by Boyden chamber system. The SCID mice intraperitoneally injected with 4 × 10^7 hu-PBL and subcutaneously injected with 3 × 10^6 T24-3 cells were named hu-PBL-T24-3-SCID model. Human IgG level in the blood plasma of mice was detected by ELISA, and human CD3^＋, CD4^＋, CD8^＋ T cells in blood and spleen cells of mice were detected by FCM analysis for human immune reconstruction study. Human CK20 mRNA expression in mice peripheral blood was detected by RT-PCR to investigate metastasis of tumor cells. The PBMCs were isolated from human peripheral blood, and were induced into DCs by co-culture with rhGM-CSF and rhlL-4 in vitro. The DC vaccines were produced by co-culturing with whole tumor antigen which was purified through freezing and melting T24-3 cell subset. After T24-3 cells injected into SCID mice for 5 weeks, the mice were treated with DC vaccines. Results： All mice were initially treated at 5th week. The expression of CK20 mRNA in peripheral blood of DC vaccines treated mice was the lowest. There was 2 mice showing CK20 mRNA expression and 3 mice with metastasis tumor in PBS group. MMP-7 mRNA expression in tumor tissues of DC vaccines treated mice was statistically lower than that of PBS group （P 〈 0.01）. Conclusion： DC vaccines have a good effect on hu-PBL-SCID mice bladder cancer model by reducing hematogenous micrometastasis.

Role of Dendritic Cells in Myocarditis Induced by Coxsackie B_3 Virus in Mouse

Background and Objectives Autoimmune reaction may play an important role in the pathogenesis and progress in virus myocarditis. Dendritic cells are the initiators of immune reaction to foreign antigens and are considered to be key players in the induction and maintenance of autoimmune reactions. This study was undertaken to investigate the role of DC in mice with virus myocarditis. Methods and Results Fifty Balb/c mice were injected Coxsackie B3 virus to induce myocarditis and ten mice were injected culture liquid as control group. The hearts of virus - infected mice were harvested on day 3, 7, 14, 28 after the injection. All the hearts were sliced to do HE staining, MHC Ⅱ antigen and S - 100 protein immunohistochemical staining. The inflammation response and expression of MHC Ⅱ antigen and S - 100 protein positive stained cells were observed. The MHC Ⅱ antigen positive score were 1.42±0.95, 2.24 ±1. 00, 3. 23± 1. 16, 2. 58 ± 1. 05 respectively in group 3d, 7 d, 14 d, 28 d, which were significant different from control group(0. 50 ±0.75, P <0. 05). The S-100 positive staining cells in control group was 3. 2±1. 0. And the numbers were 6. 7 ± 1. 4 , 16. 4 ± 2. 5 , 21. 2±3. 3 , 13. 4 ± 2. 3 respectively in group 3 d, 7 d, 14 d, 28 d, and there were significant differences compared with the control group ( P < 0. 01) . Conclusions Immune reaction was involved in the pathogenesis in Coxsackie B3 virus - induced myocarditis in mouse, and dendritic cell might play an important role in the immune reaction.

T细胞免疫反应载体疫苗在人类疾病预防和治疗中的应用

人类疾病,特别是传染病和癌症,对公共卫生安全和全球经济构成前所未有的挑战。预防和治疗性疫苗的开发是应对人类疾病的优先对策。本文综述了疫苗载体的免疫学原理、T细胞载体疫苗设计策略及疫苗研究进展,为新型疫苗的设计提供新的思路。T细胞可以在机体发生感染后分化成不同的效应T细胞群,它们可以起到清除病原体的作用,关于效应T细胞功能和机制的研究对于设计能够引发基于T细胞免疫的疫苗至关重要。目前很多病毒(例如HIV、HCMV感染)和肿瘤疫苗的研发都侧重于T细胞类疫苗,在所有疫苗种类中,激活T细胞免疫反应的载体疫苗具有显著优势。许多来源的载体,包括病毒载体、细菌载体和核酸载体,它们在抗原提呈能力、免疫原性和保护效力方面都有良好的表现。此外,还总结了T细胞载体疫苗设计的策略,包括确定适当的抗原提呈途径和载体递送途径、确保生物安全性、如何选择合适的疫苗的载体、各种载体疫苗的优缺点等,尤其是mRNA疫苗在应对新冠疫情中发挥了重要的作用。疫苗载体的技术进步将会加速新型疫苗的研发,并且能促进人们对突发公共卫生事件的应对。