B7-1 Antigen ; B7-2 Antigen ; Hematologic Neoplasms ; Humans

OBJECTIVETo investigate the trichostain A (TSA)-induced expression of costinmulatory molecules CD80 and CD86 in HL-60, K562 and mononuclear cells (MNC) of bone marrow in AML patients and its clinical significance.

METHODSThe TSA-induced expression of costimulatory molecules CD80, CD86 in HL-60, K562 and BMMNC, and the cell viability were detected by flow cytometry; the mRNA expression of CD80 and CD86 was detected by RT-PCR; after the TSA-induced HL-60 cells and K562 cells were irradiated with 75 Gy, the effect of these cells on proliferation of PBMNC from healthy volunteers was determined with CCK-8 method.

RESULTSThe HL-60 cells and BMMNC in AML patients expressed CD86, not expressed CD80, while the K562 cells not expressed CD86 and CD80. TSA could up-regulate the expression of CD86 in HL-60 cells and BMMNC of AML patients. The TSA-induced HL-60 cells expressing costimulatory molecule CD86 showed the proliferative effect on BMMNC from healthy volunteers.

CONCLUSIONThe TSA can induce the expression of costimulatory molecule CD86 in HL-60 cells and BMMNC in AML patients, and can improve the proliferation of PBMNC in healthy volunteers.

B7-1 Antigen ; B7-2 Antigen ; Cell Line, Tumor ; Cell Survival ; Flow Cytometry ; Humans ; Hydroxamic Acids ; Leukemia, Myeloid, Acute

Bladder urothelial carcinoma(BUC)is a common malignant tumor in the urinary system.Pt-based chemotherapy has long been a standard therapeutic method for resectable or metastatic BUC,but with poor outcomes.Immune checkpoint inhibitors specific to programmed death 1(PD-1)/programmed death-ligand 1(PD-L1)and cytotoxic T lymphocyte-associated protein 4(CTLA-4)pathways have shown significant antitumor activities,safety,and enduring reactivity in clinical trials,thus creating a new epoch for the treatment of advanced-stage BUC.This article reviews the relationships of BUC with PD-1/PD-L1 and CTLA-4 pathways,as demonstrated in clinical trials.In particular,the authors elucidate the clinical studies on the application of immune checkpoint inhibitors in different BUC stages and their optimal combining strategies,with an attempt to improve the clinical use of immune inhibitors for BUC treatment.
Apoptosis ; B7-H1 Antigen ; CTLA-4 Antigen ; Immunotherapy ; Programmed Cell Death 1 Receptor ; Signal Transduction

OBJECTIVETo explore the role and mechanism of B7 molecules in T cell anergy.

METHODSAnti-B7-1 (CD(80)) and anti-B7-2 (CD(86)) monoclonal antibodies were used to induce T cell anergy. T cell proliferation were assayed by mixed lymphocyte reaction (MLR) with (3)H-TdR incorporation, and cytokine mRNA transcripts were analyzed with reverse transcriptase-polymerase chain reaction (RT-PCR). B7-transfected-CHO cells were used as artificial antigen presentation cells (APCs) in MLR to exclude the effects of other costimulatory molecules.

RESULTSMLR results showed that the proliferation of T cells was inhibited to various extents by anti-CD(80) or anti-CD(86) monoclonal antibody, the effect of anti-CD(86) antibody was greater than that of anti-CD(80) antibody, and the proliferation was totally blocked when the two were used together. The results of RT-PCR demonstrated that IL-2 and IFN-gamma mRNA transcripts decreased whereas IL-4 mRNA transcripts increased in T cell after treatment with anti-B7 antibo-dies for 24 hours. In MLR with artificial APC, signal one (DR7) alone could stimulate T cell proliferation at a certain threshold intensity. Costimulator B7-1 molecule could help signal one in T cell proliferation. This effect was blocked by anti-CD(80).

CONCLUSIONB7 molecules play an important role in T cell immune response. Blockade of B7 family resulted in T cell anergy. The role of CD(86) may be more important than that of CD(80). The conversion of cytokine profile from Th1's to Th2's reflected that anergetic T cells were differentiated into Th2 cells by anti-B7 suggesting that anergetic blockade of costimulator molecules may be one of the mechanisms of T cell.

Animals ; Antigens, CD ; genetics ; B7 Antigens ; B7-1 Antigen ; metabolism ; Cricetulus ; Lymphocyte Activation ; immunology ; Membrane Glycoproteins ; T-Lymphocytes ; immunology

OBJECTIVETo explore the expression of B7 co-stimulator in human malignant hematological cell lines and its significance.

METHODSAmplified and purified plasmid DNA was transfected by liposome and detection of B7 gene expression by flow cytometry and RT-PCR.

RESULTEight human malignant hematological cell lines U937, K562, CEM, Daudi, GM, PEER, Jurkat, Raji express high level of HLA molecules, low or undetectable level of B7-1 gene, and high level of B7-2 gene. Expression level of B7-1 gene was enhanced after B7-1 transfection. T cell expressed high level of IL-2 mRNA after B7-1 transfection.

CONCLUSIONMultiple human malignant hematological cell lines express low or undetectable level of B7-1 gene, suggesting that B7-1 plays a critical role in tumor immunity.

B7-1 Antigen ; Cell Line ; Flow Cytometry ; Humans ; Interleukin-2 ; T-Lymphocytes ; immunology ; Transfection ; U937 Cells

Cross-priming is an important mechanism to activate immune response, which includes two classical signal pathways. Co-stimulatory signals are essential in the effective activation and B7-family is considered to be one of the most important factor in immunotherapy. PD-L1 is a new member of B7 family, whose ligand is PD-1. PD-1/PD-L1 can down-regulate the activation of immune response, which has become a focus of research. This article reviewed the expression of PD-1/PD-L1 in normal tissue and tumor, focusing on the status of PD-1/PD-L1 pathway study in leukemia, lymphoma, multiple myeloma, aplastic anemia and so on, in order to provide a new way for treatment of hematologic diseases.
B7-H1 Antigen ; metabolism ; Hematologic Diseases ; metabolism ; Humans ; Programmed Cell Death 1 Receptor ; metabolism ; Signal Transduction

Abstract　　Tumor cells avoid immune surveillance by overexpressing ligands of checkpoint receptors on tumor cells or adjacent cells, resulting in inability or exhaustion of T cells. Numerous studies have shown that lymphoma cells highly expressed programmed cell death ligand-1 (PD-L1), suggesting that PD-1 may become an important target for lymphoma treatment. By targeting the PD-1 protein, the cellular activity of T cells will be significantly enhanced, and the tumor growth will be inhibited. Recently, antibodies against PD-1 have shown high efficacy and safety in the clinical studies of lymphoma, which are expected to become the targeted therapeutic drugs for lymphoma. In order to deeply understand the application of PD-1 antibody in treatment of lymphoma, this review briefly summaries the present state of lymphoma studies, the action mechanism and preparation method of PD-1 antibody in clinical treatment of lymphoma.
Antibodies, Monoclonal ; Apoptosis ; B7-H1 Antigen ; Humans ; Lymphoma ; Programmed Cell Death 1 Receptor

OBJECTIVE: To analyze the changes of DC subsets and the expression of CD80 and CD86 in peripheral blood of ITP patients and their correlation with dexamethasone efficacy. METHODS: Peripheral blood sample of 80 cases of ITP and 20 normal controls from June 2015 to June 2017 in our hospital were retrospectively analyzed. The specific distribution of DC subsets in the peripheral blood of all the subjects was detected by flow cytometry, and the expressions of CD80 and CD86 were detected by ELISA. RESULTS: The proportion of DC2 in DC subsets of ITP patients before treatment was significantly higher than that in normal control group (P<0.05). The proportion of DC2 in DC subset of ITP patients was still significantly higher than that of the control group (P<0.05). The level of CD80 expression on DC1 and DC2 in ITP patients before treatment was significantly higher than that in the normal control group (P<0.05), and the expression level of CD86 on DC2 was significantly higher than that of the normal control group (P<0.05). Both IL-2 and IFN- γ levels in the patients before the treatment were significantly higher than those in the normal control group (P<0.05), and the expression levels after treatment with dexamethasone decreased significantly. Before treatment, both IL-4 and IL-10 levels in ITP patients were significantly lower than those in the normal control group (P<0.05), and their expression levels after treatment with dexamethasone significantly increased (P<0.05). CONCLUSION The incidence of ITP patients closely relates with the level and dysfunction of DC subsets in peripheral blood and the expression levels of IL-2, IL-4, IL-10, IFN- γ, which significantly correlates with the efficacy of dexamethasone.
B7-1 Antigen ; Dendritic Cells ; Dexamethasone ; Humans ; Inosine Triphosphate ; Retrospective Studies

Defective dendritic cell (DC) functions have been implicated in ITP. The purpose of this study was to investigate the distribution and activation of dendritic cells in immune thrombocytopenia (ITP) patients. ITP patients were divided into 3 groups: the newly diagnosed, refractory and effective treatment group. The distributions of plasmacytoid dendritic cells (pDC) and myeloid dendritic cells (mDC) in peripheral blood, bone marrow and spleen were detected with flow cytometry. The expression level of CD80 and CD86 on surface of pDC and mDC was also detected with flow cytometry. The results indicated that the percentage of mDC was higher than that of pDC in all sites of all groups. The percentage of mDC and pDC in all site of refractory group was higher than that in newly diagnosed and effective groups, but the percentage of mDC in spleen of refractory group was obviously higher than that in other sites. The percentage of pDC was no significant different in all groups. The expression level of CD86 in all groups was higher than that of CD80, the expression level of CD80 was lower in mDC and pDC of all groups, but there was no obvious difference in all sites. The CD86 expression in all site of refractory group was higher than that in newly diagnosed and effective treatment groups, while the CD86 expression of mDC in spleen of newly diagnosed group obviously higher than that in other sites. It is concluded that the distribution abnormality of mDC and pDC exists in ITP patients, the mDC are more accumulated in spleen, and differentiation of mDC to maturity is more obvious in spleen, spleen-derived mDC significantly express CD86, spleen-derived mDC may play an important role in the pathogenesis of ITP.
Adult ; B7-1 Antigen ; metabolism ; B7-2 Antigen ; metabolism ; Dendritic Cells ; cytology ; immunology ; Female ; Humans ; Male ; Purpura, Thrombocytopenic, Idiopathic ; immunology ; Spleen ; cytology

The objective of study was to investigate the expressions of CD80, CD86 and its ligand CD28 on peripheral lymphocytes in patients with idiopathic thrombocytopenic purpura (ITP), to explore the effect of interleukin 18 (IL-18) and its clinical significance in ITP. The expressions of co-stimulatory molecules (CD80, CD86 and its ligand CD28) on peripheral lymphocytes from 34 ITP patients and 34 normal humans were detected by immunofluorescence and flow cytometry. The IL-18 in the plasma was detected by using enzyme linked immunosorbent assay (ELISA). The results showed that the expressions of CD80 and CD86 on peripheral lymphocytes from ITP patients were higher than that of the normal control (4.21 +/- 2.27%, 7.19 +/- 5.16% vs 2.34 +/- 0.87%, 4.08 +/- 1.96%) (P < 0.01); the concentration of IL-18 in plasma of ITP patients was (538.31 +/- 111.33) pg/ml, but the concentration of IL-18 in plasma of controls was (489.44 +/- 49.07) pg/ml. The level of IL-18 negatively correlated with the platelet counts in peripheral blood (r = -0.395, P < 0.05). It is concluded that the CD28/CD80 and CD28/CD86 costimulatory molecules are overexpressed, when the IL-18 level in ITP patients is obviously higher than that in normal controls. When ITP occurred, and the co-stimulatory molecules CD80 and CD86 are closely associated with ITP, it seems that IL-18 may play an important role in ITP pathogenesis.
B7-1 Antigen ; metabolism ; B7-2 Antigen ; metabolism ; CD28 Antigens ; metabolism ; Humans ; Interleukin-18 ; blood ; Lymphocytes ; metabolism ; Purpura, Thrombocytopenic, Idiopathic ; blood ; immunology