Natural killer cells 56bnght16- have higher counts in the umbilical cord blood than in the adult peripheral blood

ABSTRACT Introduction and hypothesis: Umbilical cord blood (UCB) is an alternative source of hematopoietic stem cells for allogeneic hematopoietic stem cell transplantation in the absence of a compatible donor. The UCB transplantation has a lower incidence of chronic graft versus host disease (GvHD), but is associated with slower engraftment and slower immune reconstitution, compared to other sources. Dendritic cells (DCs) and Natural Killer cells (NKs) play a central role in the development of GvHD and the graft versus leukemia (GvL) effect, as well as in the control of infectious complications. Method: We quantified by multiparametric flow cytometry monocytes, lymphocytes, NK cells, and DCs, including their subsets, in UCB samples from 54 healthy newborns and peripheral blood (PB) from 25 healthy adult volunteers. Results: In the UCB samples, there were higher counts of NK cells 56bright16- (median 0.024 × 109/L), compared to the PB samples (0.012 × 109/L, p < 0.0001), NK 56dim16bright (median 0.446 × 109/L vs. 0.259 × 109/L for PB samples, p = 0.001) and plasmacytoid dendritic cells (pDCs, median 0.008 × 109/L for UCB samples vs. 0.006 × 109/L for PB samples, p = 0.03). Moreover, non-classic monocyte counts were lower in UCB than in PB (median 0.024 × 109/L vs. 0.051 × 109/L, respectively, p < 0.0001). Conclusion: In conclusion, there were higher counts of NK cells and pDCs and lower counts of non-classic monocytes in UCB than in PB from healthy individuals. These findings might explain the lower incidence and severity of chronic GvHD, although maintaining the GvL effect, in UCB transplant recipients, compared to other stem cell sources.

Research progress in plasmacytoid dendritic cells in systemic sclerosis / 中华微生物学和免疫学杂志

Plasmacytoid dendritic cells (pDCs) are a unique subset of dendritic cells that can rapidly produce large amounts of type Ⅰ interferon after activation. They are critical in antiviral immunity and involved in the initiation and development of many autoimmune diseases. Systemic sclerosis (SSc) is an autoimmune disease characterized by immune dysregulation, vasculopathy and progressive fibrosis of the skin and internal organs. Recent studies have found that pDCs are involved in the pathogenesis of SSc. Inhibiting the function of pDCs can effectively prevent inflammation and fibrosis in SSc, highlighting the role of pDCs in the pathogenesis of SSc. Therefore, an in-depth understanding of pDCs and their role in the pathogenesis of SSc is important for the development of pDCs and their mediators as therapeutic targets for SSc.

Clinical Characteristics and Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical manifestations, diagnosis, treatment and prognosis of blastic plasmacytoid dendritic cell neoplasm(BPDCN).@*METHODS@#The clinical features, bone marrow morphology and immunophenotyping, treatment and prognosis of 4 patients with BPDCN were analyzed retrospectively.@*RESULTS@#4 patients had bone marrow， spleen and lymph nodes involvement， 2 patients had skin lesions， and 3 patients had central nervous system infiltration． Tailing phenomenon of abnormally cells could be seen in bone marrow. The immunophenotyping showed that CD56, CD4 and CD123 expression was observed in 4 patients， and CD304 in 3 patients． One patient refused chemotherapy and died early. Both patients achieved complete remission after the initial treatment with DA+VP regimen, 1 of them achieved complete remission after recurrence by using the same regimen again． One patient failed to respond to reduced dose of DA+VP chemotherapy, and then achieved complete remission with venetoclax+azacitidine.@*CONCLUSION@#The malignant cells in BPDCN patients often infiltrate bone marrow, spleen and lymph nodes, and have specical phenotypes, with poor prognosis. The treatment should take into account both myeloid and lymphatic systems. The treatment containing new drugs such as BCL-2 inhibitors combined with demethylation drugs is worth trying.

Clinical Analysis of Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical characteristics, treatment, and prognosis of patients with blastic plasmacytoid dendritic cell neoplasm(BPDCN).@*METHODS@#Clinical data of 5 patients diagnosed with BPDCN in Wuhan First Hospital and Wuhan Tongji Hospital from June 2016 to November 2021 were retrospectively analyzed.@*RESULTS@#Among the 5 patients, 3 were male and 2 were female, with a median age of 28(10-52) years old. Four patients showed obvious skin damage at the initial diagnosis; the other one showed clinical manifestations of acute leukemia rather than obvious skin damage at the initial diagnosis, but infiltrated skin when the disease relapsed after treatment. Other infiltration sites of lesions included bone marrow (2/5), peripheral blood (2/5), lymph nodes (3/5), liver and spleen (2/5). All patients had no clinical manifestation of central nervous system infiltration. Tumor cell specific immune markers CD4, CD56, CD123 were all positive, and the median Ki-67 index was 70%. TET2, ASXL1 and NRAS gene mutations were found respectively in 3 patients by next-generation sequencing technique (NGS). ALL-like, AML-like and invasive NK/T cell lymphoma-like first-line induction chemotherapy regimens were used for the patients. One patient died of severe complications during the early stage of chemotherapy, 3 patients were evaluated as CR, and 1 patient was evaluated as PR. 2 patients were recurred and progressed after induction of chemotherapy, and one of them was evaluated as CR after re-treatment. One patient received autologous hematopoietic stem cell transplantation (auto-HSCT) and got long-term survival (OS 87 months). 3 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which one died of transplantation related complications, and 2 cases survived. The median follow-up time of 4 patients with evaluable efficacy was 28.5(9-84) months, the median OS time was 31.5(10-87) months.@*CONCLUSION@#BPDCN is a highly heterogeneous malignant tumor with a poor prognosis. HSCT, especially allo-HSCT can significantly improve the prognosis of BPDCN patients.

Blastic plasmacytoid dendritic cell neoplasm: A clinico-pathological retrospective analysis of thirteen cases / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinicopathological features of blastic plasmacytoid dendritic cell neoplasm (BPDCN).@*METHODS@#A total of 13 cases of BPDCN diagnosed in Peking University First Hospital from January 2013 to March 2022 were collected. The clinical features, histopathological characteristics, immunophenotypes and prognosis of the patients were analyzed retrospectively, and the related literatures was reviewed as well.@*RESULTS@#Among the 13 patients, 11 were male and 2 were female, with a median age of 62 years (ranging from 5 to 78 years). Among them, single organ involvement occurred in 5 cases, all of which presented with skin lesions. Two or more organs were involved in other 8 cases (single organ with bone marrow involved in 3 cases; skin, bone marrow and lymph node involved simultaneously in 3 cases; skin, bone marrow, lymph node and spleen involved simultaneously in 2 cases). Histopathologically, it was characterized by the proliferation of medium to large atypical blastic cells, which infiltrated the whole thickness of dermis. When involved, the bone marrow lesions mainly appeared in a diffuse pattern, while the lymph node structure was usually destroyed, and the red pulp of the affected spleen was diffusely invaded. Immunohistochemical staining showed that all the 13 cases were positive for CD4, CD56, and CD123 (13/13) in varying degrees. All the 9 cases expressed TCL1 (9/9). Variable expression of CD68 (KP1) (8/13), TdT (7/12), CD117 (2/6), and high Ki-67 proliferation index (40%~80%) were showed. The neoplastic cells lacked expressions of CD20, CD3, MPO, CD34, or CD30; EBER in situ hybridization were negative (0/9). After definite diagnosis, 6 cases received chemotherapy, among which 1 received adjuvant radiotherapy, and 2 received subsequent bone marrow transplantation. Another 2 cases only received maintenance treatment. The median follow-up time was 14 months (ranging from 6 to 36 months), 5 patients died of the disease (6 to 18 months), 3 patients survived (7 to 36 months up to now), and the remaining 5 patients lost follow-up.@*CONCLUSION@#BPDCN is a rare type of malignant lymphohematopoietic tumor with aggressive behavior and poor prognosis. The diagnosis should be made combining clinical features, histopathology, and immunohistochemical phenotype. Attention should be paid to differentiating BPDCN from other neoplasms with blastoid morphology or CD4+CD56+ tumors.

Chemotherapy Combined with Venetoclax Followed by Allo-Hematopoietic Stem Cell Transplantation for Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy and safety of chemotherapy combined with venetoclax followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN).@*METHODS@#The clinical data of 3 patients with BPDCN undergoing allo-HSCT in Department of Hematology, Wuhan First Hospital from July 2017 to November 2021 were collected and retrospectively analyzed.@*RESULTS@#Among the 3 patients, there were 1 male and 2 females, aged 27-52 years old. Skin lesions were observed during initial diagnosis, and it could also be characterized by acute leukemia. Characteristic molecular markers of tumor cells, such as CD4, CD56, CD123, and CD303 were positive. In addition, the expression detection of Bcl-2 in 3 patients were positive. Chemotherapy combined with venetoclax in the initial induction of chemotherapy (1 case) or disease recurrence and progress (2 cases) was performed. There were 2 cases evaluated as complete remission (CR) and 1 case as partial remission (PR) before allo-HSCT. The patients all received a nonmyeloablative conditioning without total body irradiation (TBI). The prevention programme of graft-versus-host disease (GVHD) was antithymocyte globulin + mycophenolate mofetil + cyclosporin A/FK506 ± methotrexate. The number of mononuclear cell (MNC) count was (16.73-18.35)×108/kg, and CD34+ cell count was (3.57-4.65)×106/kg. The 3 patients were evaluated as CR after allo-HSCT (+21 to +28 d), the donor-recipient chimerism rate was 100%, and Ⅲ-Ⅳ GVHD was not observed. One patient died at +50 d after transplantation, two patients were followed up for 28 months and 15 months, respectively, and achieved disease-free survival (DFS).@*CONCLUSIONS@#BPDCN is a highly aggressive malignant tumor with poor prognosis. Chemotherapy combined with venetoclax followed by allo-HSCT may lead to long-term DFS or even cure. Post-transplant maintenance is still unclear.

Effect of Plasmacytoid Dendritic Cell Dose in Grafts on CMV Infection after Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To investigate the correlation between plasmacytoid dendritic cell (pDC) dose in grafts and the occurrence of cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*METHODS@#The clinical data of 80 children who received allo-HSCT in Children's Hospital of Soochow University from August 20, 2020 to June 11, 2021 were retrospectively analyzed. Proportions of DC subsets and T-cell subsets in grafts were detected by flow cytometry in order to calculate infused cell dose of each cell. Weekly monitoring of CMV-DNA copies in peripheral blood for each child were performed after transplantation. The last follow-up date was December 31, 2021.@*RESULTS@#All the children gained hematopoietic reconstitution. CMV infection was observed in 51 children (63.8%±5.4%) within the first 100 days after transplantation, including 2 cases developing CMV disease. Univariate analysis indicated that infused doses of DC and pDC were significantly associated with CMV infection within 100 days after allo-HSCT (P <0.05). Multivariate analysis indicated that a high dose infusion of pDC was an independent protective factor for CMV infection within 100 days after allo-HSCT (P <0.05). By the end of follow-up, 7 children died of transplantation-related complications, including 2 deaths from CMV disease, 2 deaths from extensive chronic graft-versus-host disease, and 3 deaths from capillary leak syndrome. The overall survival rate was 91.2%.@*CONCLUSION@#The pDC in grafts may be associated with early infection of CMV after allo-HSCT, while a high infused pDC dose may serve as a protective factor for CMV infection after transplantation.

Application study on adoptive transfusion of tolerogenic dendritic cells in promoting immune tolerance of liver transplantation in rat models / 器官移植

Objective To investigate the role of tolerogenic dendritic cell (tolDC) in inducing immune tolerance in liver transplantation. Methods Liver transplantation rat models of spontaneous tolerance [Brown Norway (BN)→Lewis, tolerance group, n=6] and acute rejection (AR) (Lewis→BN) were established. In AR rat models, tolDC transfusion was performed in the study group (tolDC group, n=6) and no intervention was given in the control group (AR group, n=6). The survival time of rats in each group was observed. The transplant liver tissues of rats were prepared for pathological examination in each group. The expression of myeloid dendritic cell (mDC) and plasmacytoid dendritic cell (pDC) in rat peripheral blood, transplant liver, spleen and lymph nodes in each group was detected by flow cytometry. The expression levels of serum interleukin (IL)-10 and interferon (IFN)-γ in each group were measured by enzyme-linked immune absorbent assay. Results Pathological manifestations of rats in the AR group mainly included inflammatory cell infiltration and tissue structural disorder in transplant liver, and the survival time was 7-14 d. In the tolDC and tolerance groups, the transplant liver tissues were almost normal, and the longest survival time exceeded 100 d. Compared with the AR group, the expression levels of CD11+mDC in peripheral blood, transplant liver, spleen and lymph nodes of rats were significantly down-regulated in the tolerance and tolDC groups (all P < 0.05), and those of CD86 and major histocompatibility complex (MHC)Ⅱon the surface of CD11+mDC were also significantly down-regulated (all P < 0.05). Compared with the AR group, the expression levels of pDC in peripheral blood, transplant liver, spleen and lymph nodes of rats were significantly up-regulated in the tolerance and tolDC groups (all P < 0.05), whereas those of MHCⅡon the surface of pDC were all significantly down-regulated (all P < 0.05). Compared with the AR group, the expression levels of serum IL-10 were significantly up-regulated, and IFN-γ were significantly down-regulated in the tolerance and tolDC groups (all P < 0.05). Conclusions As tolDC subsets, mDC and pDC play a positive role in regulating the incidence of graft immune tolerance in rats after liver transplantation.

Uncommon plasmacytoid myoepithelioma originating from ectopic minor salivary gland in neck: a rare case with rare site presentation

The aim of this case report is to present as case of plasmacytoid at ectopic minor salivary gland in the neck which is a rare neoplasm with uncommon presentation of site. Usually it is a tumor of major salivary gland and more common in parotid gland and less common in the minor salivary gland of the oral cavity predominantly in palate. Here authors are discussing a case of 10-year-old female who presented in our institute with complain of swelling over right mid cervical region which was clinically suspected as reactive cervical lymph node. Patient was evaluated further and cytologically diagnosed as a case of plasmacytoid myoepithelioma. It was also confirmed as a case of plasmacytoid myoepithelioma after histopathology and immunohistochemistry studies. Plasmacytoid myoepithelioma at ectopic minor salivary gland site in the neck is uncommon presentation and only a limited number of cases have been reported in literature.

A case report of plasmacytoid urothelial carcinoma of the ureter / 中华泌尿外科杂志

Primary ureteral plasmacytoid carcinomas is a rare tumor with high grade and poor diagnosis. Pathological and immunohistochemical staining play an extremely key role in diagnosis since there is no specific clinical and radiological evidence. The surgical removement is the first line treatment. Herein, we report a case of ureteral plasmacytoid carcinoma that was well controlled with multimodal therapy.

A case report of plasmacytoid urothelial carcinoma of the ureter / 中华泌尿外科杂志

Primary ureteral plasmacytoid carcinomas is a rare tumor with high grade and poor diagnosis.Pathological and immunohistochemical staining play an extremely key role in diagnosis since there is no specific clinical and radiological evidence.The surgical removement is the first line treatment.Herein,we report a case of ureteral plasmacytoid carcinoma that was well controlled with multimodal therapy.

Pleomorphic Adenoma of the Upper Lip: A Rare Presentation in a Young Boy and Differential Diagnosis

@#A healthy 4-year-old boy presented with a painless lump on his upper lip for three years duration with no significant changes in size. Clinical examination revealed the presence of firm and mobile lump on the labial mucosa measuring approximately 15 mm × 10 mm, slightly pale yellowish compared to the surrounding tissues. The covering mucosa was intact and was non-tender upon palpation. Excisional biopsy was performed under general anaesthesia and the histopathological results revealed the presence of a partially encapsulated pleomorphic adenoma with variable epithelial and stromal components.

Arsenic trioxide induces regulatory functions of plasmacytoid dendritic cells through interferon- inhibition

Arsenic trioxide (AsO) is recently found to have therapeutic potential in systemic sclerosis (SSc), a life-threatening multi-system fibrosing autoimmune disease with type I interferon (IFN-I) signature. Chronically activated plasmacytoid dendritic cells (pDCs) are responsible for IFN-I secretion and are closely related with fibrosis establishment in SSc. In this study, we showed that high concentrations of AsO induced apoptosis of pDCs mitochondrial pathway with increased BAX/BCL-2 ratio, while independent of reactive oxygen species generation. Notably, at clinical relevant concentrations, AsO preferentially inhibited IFN- secretion as compared to other cytokines such as TNF-, probably due to potent down-regulation of the total protein and mRNA expression, as well as phosphorylation of the interferon regulatory factor 7 (IRF7). In addition, AsO induced a suppressive phenotype, and in combination with cytokine inhibition, it down-regulated pDCs' capacity to induce CD4 T cell proliferation, Th1/Th22 polarization, and B cell differentiation towards plasmablasts. Moreover, chronically activated pDCs from SSc patients were not resistant to the selective IFN- inhibition, and regulatory phenotype induced by AsO. Collectively, our data suggest that AsO could target pDCs and exert its treatment efficacy in SSc, and more autoimmune disorders with IFN-I signature.

Neoplasia blástica de células dendríticas plasmocitoides variante leucemia aguda: reporte de un caso / Blastic plasmacytoid dendritic cell neoplasm variant acute leukemia: case report

RESUMEN La neoplasia blástica de células dendríticas plasmocitoides (NBCDP) es una malignidad hematológica poco frecuente y generalmente agresiva, por lo cual se requiere su reconocimiento precoz. A continuación, se describe el curso clínico prolongado de un paciente masculino de 60 años con NBCDP procedente de Venezuela, en cuyos hallazgos más relevantes destacó la presencia de lesiones cutáneas, organomegalias, infiltración de la médula ósea y del sistema nervioso central. Posterior al diagnóstico se indicó quimioterapia sistémica, no obstante, el paciente falleció por complicaciones respiratorias durante la fase de inducción del tratamiento. En esta enfermedad es necesario establecer el diagnóstico diferencial con trastornos linfoproliferativos, leucemias linfoides y mieloides agudas, constituyendo el análisis morfológico de las células neoplásicas un aspecto importante para una adecuada orientación diagnóstica.

ABSTRACT Blastic plasmacytoid dendritic cell blast neoplasm (BPDCN) is a rare and generally aggressive hematologic malignancy, requiring early recognition. Below is a description of the prolonged clinical course of a 60-year-old male patient with BPDCN from Venezuela, whose most relevant findings highlighted the presence of skin lesions, organomegaly, infiltration of the bone marrow and central nervous system. Systemic chemotherapy was prescribed after diagnosis; however, the patient died of respiratory complications during the induction phase of treatment. In this disease, it is necessary to establish the differential diagnosis with lymphoproliferative disorders, acute lymphoid and myeloid leukemias. The morphological analysis of neoplastic cells is, thus, an important aspect toward proper diagnostic guidance.

Plasmacytoid Urothelial Carcinoma of the Bladder: Case Report and Review of the Literature / Carcinoma urotelial de vejiga, variante plasmocitoide: Reporte de un caso y revisión de la literatura

Introduction Plasmacytoid urothelial carcinoma (PUC) of the bladder is a rare histological variant, accounting for 1 to 3% of the invasive urothelial carcinomas, and it is typically aggressive. So far, it has not been well characterized, and the literature is based on reports and case series. Case Report A 70-year-old male patient presenting with 4 months of constitutional and urinary symptoms, with an ultrasound finding of bilateral hydronephrosis and diffuse thickening of the bladder walls. In the cystoscopy, trigone of infiltrated appearance, a biopsy wass performed, whose immunohistochemistry revealed a PUC. The abdominopelvic image showed an infiltrative lesion that compromised the muscle of the bladder and extended to the perivesical fat, without adequate plane of cleavage with the prostate and a single hypogastric adenopathy suspected of malignancy. It was classified as cT3b vs cT4aN1M0 (chest computed tomography [CT] negative for malignancy), and the patient was submitted to a radical cystoprostatectomy, extended pelvic lymphadenectomy and non-continent urinary diversion with ileal conduit. The pathology revealed a diffuse PUC with prostatic stromal involvement and 22 of 39 lymph nodes positive for malignancy. Finally, the patient presented a series of postoperative complications and died. Conclusion Plasmacytoid urothelial carcinoma of the bladder is a rare entity, characterized by high aggressiveness, an advanced stage at the time of diagnosis, and a poor prognosis. Currently, an aggressive approach is recommended due to its high invasive potential.

Introducción El carcinoma urotelial plasmocitoide (CUP) de la vejiga es una variante histológica poco frecuente; representa el 1 al 3% de los carcinomas uroteliales invasivos y es típicamente agresiva. Hasta el momento no ha sido bien caracterizada, y la literatura se basa en reportes y series de casos. Reporte de Caso Paciente masculino de 70 años presentando por 4 meses síntomas constitucionales y urinarios, con hallazgo ecográfico de hidronefrosis bilateral y engrosamiento difuso de las paredes vesicales. En la cistoscopia, trígono de apariencia infiltrada, se realizó biopsia cuya inmunohistoquímica reveló un CUP. En imagen abdominopélvica, se evidenció lesión infiltrativa que comprometía la muscular de la vejiga y se extendía a la grasa perivesical, sin adecuado plano de clivaje con la próstata y un único ganglio hipogástrico sospechoso de malignidad. Se clasificó como cT3b vs cT4aN1M0 (TAC tórax negativo para malignidad) y fue llevado a cistoprostatectomía radical, linfadenectomía pélvica extendida y derivación urinaria no continente con conducto ileal. La patología reveló un carcinoma urotelial variante difusa plasmocitoide con compromiso de estroma prostático y 22 de 39 ganglios positivos para malignidad. Finalmente, el paciente presentó una serie de complicaciones posoperatorias y falleció. Conclusión El carcinoma urotelial de vejiga variante plasmocitoide es una entidad poco frecuente, caracterizada por alta agresividad, un estadio avanzado al momento del diagnóstico, y un pobre pronóstico. En la actualidad, se recomienda un enfoque agresivo dado su alto potencial invasivo.

Predictive value of peripheral blood myeloid dendritic cell in 7-day adverse cardiac events in patients with acute ST segment elevation myocardial infarction / 中国医师进修杂志

Objective To investigate the effect of peripheral blood MDC on predicting adverse cardiac events of patients with acute STEMI. Methods Thirty-nine patients with acute ST segment elevation myocardial infarction admitted in the People′s Hospital of Deyang from February 2016 to August 2017 were selected by random sampling. According to 7-day adverse cardiac events, the patients were divided into non-combination adverse cardiac events group (uncomMI group, 23 patients) and combination adverse cardiac events group (comMI group, 16 patients), and 24 healthy persons were selected as normal control group. The general situation, clinical characteristics and MDC, PDC, analysis of uncomMI group and comMI group in the 1st and 3rd day after the onset of acute ST segment elevation myocardial infarction was compared. Factors influencing adverse cardiac events in patients with acute ST segment elevation myocardial infarction were analyzed. Results The peripheral blood MDC and plasmacytoid dendritic cell (PDC) counts in patients with STEMI were significantly lower than those in normal controls in early time(at the time of day 1)(P<0.05), but the peripheral blood MDC and PDC counts in uncomMI group was not significantly different from that in normal control group at the time of day 3 (P>0.05). The peripheral blood MDC and PDC counts in comMI group were lower than those in uncomMI group and control group. The Logistic analysis showed that the elderly patients, total cholesterol (TC), MDC (at the time of day 3) were all risk factors of 7-day adverse cardiac events (P < 0.05). The receiver operating characteristic (ROC) results showed that the maximum area under curve(AUC) was 0.8286 when the MDC truncation point was 7 mg/L, and the sensitivity was 80.0% and the specificity was 85.7% . Conclusions For STEMI patients, MDC of peripheral blood is associated with 7-day adverse cardiac events. The percentage of MDC in peripheral blood of patients with acute STEMI has a certain clinical value in the diagnosis of 7-day adverse cardiac events. In addition, elderly patients with STEMI have an increased risk of 7-day adverse cardiac events.

New progression in the therapy of blastic plasmacytoid dendritic cell neoplasms / 国际肿瘤学杂志

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a kind of rare and highly invasive hematological malignancy. Because of its low incidence, there is still no consensus on its standard treatment. For young patients, high intensity chemotherapy combined with hematopoietic stem cell transplantation is often used. Elderly patients who cannot accept hematopoietic stem cell transplantation receive low intensity chemotherapy. In December 2018, tagraxofusp, a new targeted drug, was approved by the U. S. Food and Drug Administration specially for treatment-naive and previously-treated BPDCN patients (age≥2 years old). Some targeted drugs, such as venetoclax and daratumumab, have certain effects on the treatment of BPDCN. The efficacies of PD-1/PDL-1 inhibitors and anti CD123 chimeric antigen receptor T cell immunotherapy need further researches.

Functional study on plasmacytoid dendritic cells in patients with HBeAg-positive chronic hepatitis B treated with entecavir / 中华实验和临床病毒学杂志

Objective@#To investigate the correlation between the frequency and function of early plasmacytoid dendritic cells (pDC) and the treatment response in patients with HBeAg-positive chronic hepatitis B receiving entecavir (ETV).@*Methods@#Patients with HBeAg-positive chronic hepatitis B were enrolled. Antiviral therapy with ETV, serum serological markerso hepatitis B virs (HBV) infection and liver function (HBV DNA load, HBsAg/anti-HBs, HBeAg and anti-HBe levels, and ALT levels) were monitored every three months before and during treatment; the efficacy of ETV was assessed by changes in the level of HBV DNA. Peripheral venous blood was collected before treatment, at 12 weeks and 24 weeks, respectively. Flow cytometry was used to detect the frequency of peripheral blood pDC and the surface co-stimulatory molecule CD86. The baseline and early treatment (12 weeks and 24 weeks) pDC frequency and functional changes were analyzed.@*Results@#Of the 100 patients with chronic hepatitis B, 45 patients received ETV treatment and 48 weeks of follow-up. Within 48 weeks of ETV treatment, HBsAg levels decreased by 0.53±0.78 log IU/mL; HBeAg decreased by 816.61S/CO, and HBeAg seroconversion occurred in 4 cases; HBV DNA content decreased by 6.04±1.12 log IU/mL, in 33 cases (73%) the HBV DNA became undetectable, in 43 cases ALT kept normal continuously for more than 3 months. In the early stage of ETV treatment, pDC% increased significantly, CD86+ pDC%, CD86MFI and CD86ABC showed no significant changes. In ETV-treated HBV DNA responders, pDC% increased significantly, CD86+ pDC%, CD86MFI and CD86ABC showed no significant changes; HBV DNA non-responders had a significant increase in pDC%, but CD86+ pDC% decreased significantly, and CD86MFI and CD86ABC showed no significant changes. The decrease in HBsAg and HBeAg levels in ETV treated patients was not significantly associated with early pDC%, CD86+ pDC%, CD86MFI and CD86ABC changes.@*Conclusions@#ETV treatment can directly inhibit the replication of HBV DNA, but does not enhance the function of immune cells.

Anti-lung cancer effect of myeloid and plasmacytoid dendritic cell combined vaccines loaded with tumor cell lysates in vitro / 中华肿瘤杂志

Objective@#To investigate the feasibility of myeloid and plasmacytoid dendritic cell combined vaccines loaded with heat-treated Lewis lung cancer cell lysates for treatment of lung cancer in mice.@*Methods@#Bone marrow cells were induced by the recombinant mouse fms-like tyrosine kinase receptor 3 ligand (rmFlt3-L) in vitro, myeloid dendritic cells (mDC) and plasmacytoid dendritic cells (pDC) were separated by magnetic beads. The mDC, pDC, and mDC∶pDC=1∶1 were stimulated with heat-treated Lewis lung cancer cell lysates, respectively. The effects of each group on stimulating of lymphocyte proliferation and inducing of T cell to kill tumor cells in vitro were compared. The alternations of the immunophenotypes of CD80, CD86, CD40 and major histocompatibility complex Ⅱ (MHC-Ⅱ) were detected by flow cytometry. The secretion of cytokines including interlukin-12 (IL-12), interlukin-6 (IL-6), and tumor necrosis factor α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA).@*Results@#The lymphocyte proliferation in mice stimulated with mDC+ pDC group loaded with heat-treated Lewis lung cancer cell lysates was 10.80±0.66, significantly higher than 8.63±0.65 of mDC group and 7.10±0.46 pDC group under the same culture conditions, respectively (P<0.05). When the ratio of effector cells: target cells (E∶T) was 10∶1, the killing rate of the mDC+ pDC group loaded with heat-treated tumor cell lysate was 31.68%±2.93%, significantly higher than 17.44%±0.97% of mDC group and 10.29%±1.33% of pDC group, respectively (P<0.05). When the ratio of E∶T was 20∶1, the killing rate of the mDC+ pDC group loaded with heat-treated tumor cell lysate was 54.77%±3.28%, significantly higher than 35.25%±1.51% of mDC group and 15.52%±0.73% of pDC group, respectively (P<0.05). When the ratio of E∶T was 40∶1, the killing rate of the mDC+ pDC group loaded with heat-treated tumor cell lysate was 73.01%±0.91%, significantly higher than 51.36%±0.58% of mDC group and 22.65%±1.28% of pDC group, respectively (P<0.05). With the rate of E∶T increased, the killing rate also increased. The mean fluorescence intensities of surface molecules including CD80, CD86, CD40 and MHC-Ⅱ of mDC: pDC=1 group pulsed with heat-treated Lewis lung cancer cell lysates were higher than those of mDC group and pDC group. The IL-6 cytokine concentrations of mDC+ pDC group, mDC group and pDC group loaded with heat-treated Lewis lung cancer cell lysates were (586.67±52.52) pg/ml, (323.33±67.14) pg/ml and (166.67±16.07) pg/ml, respectively. The concentrations of IL-12 in each group were (2 568.75±119.24) pg/ml, (2 156.25±120.55) pg/ml and (672.92±31.46) pg/ml, respectively. The concentrations of TNF-α in each group were (789.33±48.08) pg/ml, (584.89±116.49) pg/ml and (291.56±40.73) pg/ml, respectively. The concentrations of IL-6, IL-12 and TNF-α secreted by mDC+ pDC group were much higher than those of mDC group and pDC group under the same culture conditions (P<0.05).@*Conclusions@#The mDCs and pDCs combined vaccines pulsed with heat-treated Lewis lung cancer cell lysates have synergistic effects on inducing of T lymphocyte proliferation and killing tumor cells in vitro. This synergistic anti-tumor effect is related with up-regulation of co-stimulatory molecules and increased secretion of cytokines.

New progression in the therapy of blastic plasmacytoid dendritic cell neoplasms / 国际肿瘤学杂志

Blastic plasmacytoid dendritic cell neoplasm (BPDCN)is a kind of rare and highly invasive hematological malignancy. Because of its low incidence,there is still no consensus on its standard treatment. For young patients,high intensity chemotherapy combined with hematopoietic stem cell transplantation is often used. Elderly patients who cannot accept hematopoietic stem cell transplantation receive low intensity chemo-therapy. In December 2018,tagraxofusp,a new targeted drug,was approved by the U. S. Food and Drug Administration specially for treatment-naive and previously-treated BPDCN patients (age≥2 years old). Some targeted drugs,such as venetoclax and daratumumab,have certain effects on the treatment of BPDCN. The efficacies of PD-1 / PDL-1 inhibitors and anti CD123 chimeric antigen receptor T cell immunotherapy need further researches.