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.

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.

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.

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.

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 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.

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.

Blastic Plasmacytoid Dendritic Cell Neoplasm:Progress in Cell Origin,Molecular Biology,Diagnostic Criteria and Therapeutic Approaches

Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare hematological malignancy characterized by recurrent skin nodules,an aggressive clinical course with rapid involvement of hematological organs,and a poor prognosis with poor overall survival.BPDCN is derived from plasmacytoid dendritic cells(pDCs)and its pathogenesis is unclear.The tumor cells show aberrant expression of CD4,CD56,interleukin-3 receptor alpha chain(CD 123),blood dendritic cell antigen 2(BDCA 2/CD303),blood dendritic cell antigen 4(BDCA4)and transcription factor(E protein)E2-2(TCF4).The best treatment drugs are based on experience by adopting those used for either leukemia or lymphoma.Relapse with drug resistance generally occurs quickly.Stem cell transplantation after the first complete remission is recommended and tagraxofusp is the first targeted therapy.In this review,we summarize the differentiation of BPDCN from its cell origin,its connection with normal pDCs,clinical characteristics,genetic mutations and advances in treatment of BPDCN.This review provides insights into the mechanisms of and new therapeutic approaches for BPDCN.

EXPRESSION AND SIGNIFICANCE OF TUMOR INFILTRATING DENDRITIC CELLS IN RENAL CELL CARCINOMA

Objective: To study the expression of dendritic cells in human renal cell carcinoma and explore the cause, so to reveal the mechanism of escaping immune surveillance in RCC. Methods: The expressions of CD83+DCS, CD1a+DCS,VEGF and TGF-β1 in tumoral, peritumoral and normal kidney tissues of RCC in 30 cases were detected by immunohistochemistry using streptavidin/peroxidese(SP) Results: CD83+DCS were mainly located in the peritumoral areas; whereas CD1a+DCS、were mainly retained within the cancer nests. The number of CD83+DCS was inversely correlated with the clinical stage(P<0.05); but there were no significant correlations between the number of CD1a+DCS、and the clinical stage(P>0.05). The expressions of CD83+DCS and CD1a+DCS have significant difference between the tumoral, peritumoral and normal kidney tissues(P<0.001). The expression of VEGF and TGF-β1 were significantly lower in samples with highly infiltrating CD83+DCS(P<0.05); Whereas CD1a+DCS were not (P>0.05). Conclusion: DC has the tendency to gathering in tumor, but because of the immunosuppressive cytokins, for example VEGF and TGF-β1, inhibits the maturation of DC, there are less mature TIDCS(CD83+TIDCS) in the tumoral tissues, they are mainly located in the peritumoral areas. This may contribute to the mechanism of escaping immune surveillance in RCC.

Intra-abdominal inflammatory pseudotumor-like follicular dendritic cell sarcoma associated with paraneoplastic pemphigus: A case report and review of the literature

BACKGROUD Follicular dendritic cell(FDC)sarcomas are rare neoplasms that occur predominantly in the lymph nodes.They can also occur extranodally.Extranodal FDC sarcomas most commonly present as solitary masses.Inflammatory pseudotumor(IPT)-like FDC sarcomas,a subcategory of FDC sarcomas,are rarer than other sarcoma subtypes.They are composed of spindle or ovoid neoplastic cells and exhibit an admixture of plasma cells and prominent lymphoplasmacytic infiltration.Paraneoplastic pemphigus(PNP),also known as paraneoplastic autoimmune multiorgan syndrome,is a rare autoimmune bullous disease that is associated with underlying neoplasms.PNP has a high mortality,and its early diagnosis is usually difficult.CASE SUMMARY We describe a 27-year-old woman who presented with stomatitis,conjunctivitis,and skin blisters and erosions as her first symptoms of PNP with an intraabdominal IPT-like FDC sarcoma.The patient underwent surgical tumor resection and received tapering oral corticosteroid treatment.She showed no recurrence at the 1-year follow-up.CONCLUSION IPT-like FDC sarcomas are rare underlying neoplasms that have an uncommon association with PNP.PNP-associated FDC sarcomas predominantly occur in intra-abdominal sites and suggest a poor prognosis.Surgical resection is an essential and effective treatment for PNP and primary and recurrent FDC sarcomas.

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.

Clinicopathological features and prognosis assessment of extranodal follicular dendritic cell sarcoma

AIM: To establish a model for prognosis assessment of extranodal follicular dendritic cell (FDC) sarcoma.METHODS: Nine lesions were examined by routine and molecular approaches.Clinicopathological factors from the new cases and 97 reported cases were analyzed for their prognostic values.RESULTS: The current lesions were found in f ive male and four female patients,located mainly in the head and neck area and averaging 7.2 cm in size.Six patients had recurrence or metastasis and three remained free of disease.The 106 patients (male/female ratio,1.1:1) were aged from 9 to 82 years (median,44 years).The tumor sizes ranged from 1.5 to 21 cm (mean,7.4 cm).Abdominal/pelvic region was affected most frequently (43%).Surgical resection was performed in 100 patients,followed by radiation and/or chemotherapy in 35 of them.Follow-up data were available in 91 cases,covering a period of 3-324 mo (mean,27 mo;median,19 mo).Of the informative cases,38 (42%) had recurrence or metastasis,and 12 (13%) died of the disease.These tumors were classif ied histologically into lowand high-grade lesions.A size ≥ 5 cm (P = 0.003),highgrade histology (P = 0.046) and a mitotic count ≥ 5/10 HPF (P = 0.013) were associated with tumor recurrence.The lesions were def ined as low-,intermediateand high-risk tumors,and their recurrence rates were 16%,46% and 73%,and their mortality rates 0%,4% and 45%,respectively.CONCLUSION: Extranodal FDC tumors behave like soft tissue sarcomas.Their clinical outcomes are variable and can be evaluated according to their sizes and grades.

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.

Recognition of HBV antigens and HBV DNA by dendritic cells

BACKGROUND: Hepatitis B virus (HBV) is a hepatotropic, noncytopathic, DNA virus which can cause acute and chronic infection. Viral persistence is associated with a weak or absent specific immune responses to HBV, particularly the cellular immune response. Dendritic cells (DCs) are professional antigen-presenting cells with a unique T cell stimulatory aptitude that play a crucial role in the instruction of adaptive immune responses upon infection. An impaired function of DCs was suggested by recent studies to account for the T and B cell hyporesponsiveness in chronic HBV infection. This review summarizes recent insights into the recognition of HBV antigens by DCs. DATA SOURCES: Studies were identified by searching MEDLINE and/or PubMed for articles using the key words 'hepatitis B virus (HBV)', 'dendritic cells', 'C-type lectins', 'mannose receptor', 'toll-like receptor', and 'dendritic cell-specific intercellular-adhesion-molecule-3 grabbing nonintegrin (DC-SIGN)' up to December 2009. Additional papers were identified by a manual search of the references from the key articles. RESULTS: DCs play an important role in the progress of hepatitis B, especially in the recognition of HBV. There are three main ways of recognition of HBV antigens by DCs. First, HBV DNA can be recognized by DCs through toll-like receptor 9 (TLR9) which activates the NF-kappa B signal pathway and p38 MAPK to up-regulate the expression of interferon (IFN) regulatory factor 7 (IRF-7) in a manner independent of type I IFN signaling, resulting in secretion of type I IFN and inflammatory cytokines, and induction of DC maturation and the adaptive immune response. Second, HBc/HBeAg cannot be recognized by DCs, but DNA or ssRNA encapsulated within HBcAg can be internalized by DCs through TLRs. Third, HBsAg can be internalized by DCs through the mannose receptor, which lacks the ability to induce DC maturation without the assistance of DC-SIGN. Meanwhile, there is some cross-talk among the three mechanisms, which induces an effective anti-viral response or HBV persistence. CONCLUSIONS: On the basis of these recognition processes, methods have been used to enhance the efficacy of DC-based vaccine against HBV and have been useful in the clinical application of HBV vaccine therapy. But the interactions between HBV antigens/HBV DNA and DCs are not clear, and cross-talk between TLRs and various ligands makes HBV antigen recognition by DCs more complicated. More efforts should be made to define the mechanisms and develop effective vaccines and therapies. (Hepatobiliary Pancreat Dis Int 2010; 9:584-592)

Follicular dendritic cell sarcoma of the liver:unusual presentation of a rare tumor and literature review

BACKGROUND:Hepatic follicular dendritic cell (FDC) sarcoma is an extremely rare neoplasm.Most commonly,FDC sarcoma presents as a solitary mass in lymph nodes,however,several extra-nodal locations have been identified.METHODS:We report a case of a 53-year-old female who presented with symptoms of abdominal pain,fever,anemia,and jaundice.After an extensive review of the literature,we have found only 12 cases of hepatic FDC sarcoma.RESULTS:The tumor was 11.5 cm in diameter and composed of spindle and epithelioid cells with ovoid nuclei and associated with mixed inflammatory infiltrate.Immunohistochemical stains were positive for CD35 and CD21.The patient underwent a left hepatic lobectomy.CONCLUSIONS:Liver follicular dendritic cell sarcoma is a very rare tumor.Most cases present with abdominal pain and weight loss,and most of them can be managed by hepatic resection with excellent short-term outcomes.

Antitumor immunity by a dendritic cell vaccine encoding secondary lymphoid chemokine and tumor lysate on murine prostate cancer

Aim： To investigate the antitumor immunity by a dendritic cell （DC） vaccine encoding secondary lymphoid chemokine gene and tumor lysate on murine prostate cancer. Methods： DC from bone marrow of C57BL/6 were transfected with a plasmid vector expressing secondary lymphoid chemokine （SLC） cDNA by Lipofectamine2000 liposome and tumor lysate. Total RNA extracted from SLC＋lysate-DC was used to verify the expression of SLC by reverse transcriptase-polymerase chain reaction （RT-PCR）. The immunotherapeutic effect of DC vaccine on murine prostate cancer was assessed. Results： We found that in the prostate tumor model of C57BL/6 mice, the adminstration of SLC＋lysate-DC inhibited tumor growth most significantly when compared with SLC-DC, lysate-DC, DC or phos- phate buffer solution （PBS） counterparts （P 〈 0.01）. Immunohistochemical fluorescent staining analysis showed the infiltration of more CD4＋, CD8＋ T cell and CD11c＋ DC within established tumor treated by SLC＋lysate-DC vaccine than other DC vaccines （P 〈 0.01）. Conclusion： DC vaccine encoding secondary lymphoid chemokine and tumor lysate can elicit significant antitumor immunity by infiltration of CD4＋, CD8＋ T cell and DC, which might provide a potential immunotherapy method for prostate cancer.

Mechanism of immune tolerance induced by donor derived immature dendritic cells in rat high-risk corneal transplantation

·AIM: To study the role of immature dendritic cells (imDCs) on immune tolerance in rat penetrating keratoplasty (PKP) in high -risk eyes and to investigate the mechanism of immune hyporesponsiveness induced by donor-derived imDCs. ·METHODS: Seventy-five SD rats (recipient) and 39 Wistar rats (donor) were randomly divided into 3 groups: control, imDC and mature dendritic cell (mDC) group respectively. Using a model of orthotopic corneal transplantation in which allografts were placed in neovascularized high -risk eyes of recipient rat. Corneal neovascularization was induced by alkaline burn in the central cornea of recipient rat. Recipients in imDC group or mDC group were injected donor bone marrow-derived imDCs or mDCs of 1 ×10 6 respectively 1 week before corneal transplantation tail vein. Control rat received the same volume of PBS. In each group, 16 recipients were kept for determination of survival time and other 9 recipients were executed on day 3, 7 and 14 after transplantation. Cornea was harvested for hematoxylin eosin staining and acute rejection evaluation, Western blot was used to detect the expression level of Foxp3. ·RESULTS: The mean survival time of imDC group was significantly longer than that of control and mDC groups (all 【0.05). The expression level of Foxp3 on CD4 + CD25 + T cells of imDC group (2.24 ±0.18) was significantly higher than that in the control (1.68 ±0.09) and mDC groups (1.46±0.13) (all 【0.05).·CONCLUSION: Donor -derived imDC is an effective treatment in inducing immune hyporesponsiveness in rat PKP. The mechanism of immune tolerance induced by imDC might be inhibit T lymphocytes responsiveness by regulatory T cells. ·

Dendritic cell-based immunotherapy for malignant glioma

The immunotherapy for malignant glioma faces unique difficult, due to some anatomical and immunological characteristics including the existence of blood brain barrier, the absence of lymphatic tissues and dendritic cells （DCs） in the central nervous system （CNS） parenchyma, and the presence of an immunosuppressive microenvironment. Therefore, immunothera-peutic approaches will not be beneficial unless the compromised immune status in malignant glioma patients is overcome. DC-based immunotherapy, vaccinating cancer patients with DCs pulsed with various tumor antigens, is one of the most promising immunotherapeutic approaches for treatment of malignantglioma because it seems able to overcome, at least partially, the immunosuppressive state associated with primary malignancies. The preparation of DCs, choice of antigen, and route and schedule of administration are improving and optimizing with rapid development of molecular biology and gene engineering technology. DC vaccination in humans, after a number of pre-clinical models and clinical trials, would increase the clinical benefits for malignant glioma immunotherapy.