Clinical significance of B7-H3, an expression membrane type of myeloid-derived suppressor cell in patients with acute pancreatitis / 中华急诊医学杂志

Objective To explore the clinical significance of B7 family homology factor-3 (B7-H3),an expression membrane type of myeloid-derived suppressor cell (MDSC),in patients with acute pancreatitis (AP).Methods A total of 63 patients with AP initially treated in the Emergency Department at the First Affiliated Hospital of Soochow University from January,2014 to December,2015 were selected.Of them,25 suffered from mild AP (MAP),20 had moderate AP (MSAP) and 18 had severe AP (SAP).Another 20 healthy subjects with matching age and gender served as the control group.All patients with AP conformed to the diagnostic criteria of Guidelines or Diagnosis and Treatment of Acute Pancreatitis set in 2013 in China.Patients with other underlying diseases that might influence the clinical outcomes were excluded,including those with tumors,autoimmune diseases,viral infections,trauma and other disorders.A flowcytometer was used to detect the expression rate of MDSC in peripheral venous blood and the expression of B7-H3 on MDSC membrane.The continuous monitoring was carried out for 24 h,48 h and 72 h in patients with AP.Results Compared with healthy subjects,the MDSC cells in patient groups 24 hours after AP onset increased notably (P ＜0.01) especially the highest increase in the SAP group,followed by the MSAP group and the lowest in the MAP group.There were significant differences in pairwise comparisons (P ＜ 0.05).From successive observation of each group,there was no significant difference in MDSC between the MAP group and the MSAP group 24 hours,48 hours and 72 hours after AP onset.However,MDSC reached its peak 48 hours after AP onset,but it declined 72 hours after AP onset in the SAP group (P ＜ 0.05).B7-H3 expressed significantly 24 hours after AP onset,but there was no expression of B7-H3 in the healthy group.Meanwhile,B7-H3 was expressed most highly in the SAP group,followed by the MSAP group and lowest in the MAP group.There were significant differences in expression of B7-H3 found in pairwise comparisons (P ＜ 0.05).The successive observation showed that there was no significant difference in B7-H3 expression between the MAP group and the MSAP group 24 hours,48 hours and 72 hours after AP onset.However,there was a trend of increase in B7-H3 expression as time prolonged found among 24 hours,48 hours and 72 hours after AP onset in the SAP group (P ＜ 0.05).Conclusions The expressions of MDSC and B7-H3 were high in AP,and there were significant differences in both expressions among MAP,MSAP and SAP groups.These phenomena offer clues in further understanding about the immunological disorders during AP giving better guidelines for clinical practice.

The CD28-B7 Family in Anti-Tumor Immunity: Emerging Concepts in Cancer Immunotherapy

The interactions between B7 molecules and CD28-family receptors are crucial in the regulation of adaptive cellular immunity. In cancer, the aberrant expression of co-inhibitory B7 molecules has been attributed to reduced anti-tumor immunity and cancer immune evasion, prompting the development of cancer therapeutics that can restore T cell function. Murine tumor models have provided significant support for the targeting of multiple immune checkpoints involving CTLA-4, PD-1, ICOS, B7-H3 and B7-H4 during tumor growth, and clinical studies investigating the therapeutic effects of CTLA-4 and PD-1 blockade have shown exceptionally promising results in patients with advanced melanoma and other cancers. The expression pattern of co-inhibitory B7 ligands in the tumor microenvironment has also been largely correlated with poor patient prognosis, and recent evidence suggests that the presence of several B7 molecules may predict the responsiveness of immunotherapies that rely on pre-existing tumor-associated immune responses. While monotherapies blocking T cell co-inhibition have beneficial effects in reducing tumor burden, combinatorial immunotherapy targeting multiple immune checkpoints involved in various stages of the anti-tumor response has led to the most substantial impact on tumor reduction. In this review, we will examine the contributions of B7- and CD28-family members in the context of cancer development, and discuss the implications of current human findings in cancer immunotherapy.

Emerging Co-signaling Networks in T Cell Immune Regulation

Co-signaling molecules are surface glycoproteins that positively or negatively regulate the T cell response to antigen. Co-signaling ligands and receptors crosstalk between the surfaces of antigen-presenting cells (APCs) and T cells, and modulate the ultimate magnitude and quality of T cell receptor (TCR) signaling. In the past 10 years, the field of co-signaling research has been advanced by the understanding of underlying mechanisms of the immune modulation led by newly identified co-signaling molecules and the successful preclinical and clinical trials targeting co-inhibitory molecules called immune checkpoints in the treatment of autoimmune diseases and cancers. In this review, we briefly describe the characteristics of well-known B7 co-signaling family members regarding the expression, functions and therapeutic implications and to introduce newly identified B7 members such as B7-H5, B7-H6, and B7-H7.

Changs of B7 Family Costimulatory Molecules and Their Receptors Expression in Children with Asthma / 实用儿科临床杂志

Objective To explore the possible role of B7 family cell surface costimulatory molecules and their receptors in immunopathogenesis in children with asthma.Methods Forty children with acute exacerbation of asthma and 36 cases of age-matched healthy children were enrolled in the study.Interferon(IFN-?),IFN-? and lipopolysaccharide(LPS),phorbol 12-myristate 13-acetate and ionomycin or zero were used to stimulate peripheral blood mononuclear cells,flow cytometry was used to detect B7-1 and B7-2,B7H1,B7DC and B7H expression on CD14+ cells;CD4+ cells were separated by immune beads and stimulated by phorbol-12-myristate-13-acetate and ionomycin and fluorescence quantitative polymerase chain reaction was used to detect CD28,cytotoxic lymphocyte associated antigen-4(CTLA-4),programmed death-1(PD-1)and inducible costimulator(ICOS) mRNA expression.Results 1.The levels of B7-1 and B7-2 expression in children with asthma were higher than those of healthy control group [B7-1:(6.68?3.97)% vs(1.74?0.69)%;B7-2:(10.87?5.99)% vs(1.58?0.75)% Pa