BACKGROUND T-cell checkpoint blockade and MEK inhibitor combinations are under clinical investigation. Despite progress elucidating the immuno-modulatory effects of MEK inhibitors as standalone therapies, the impact of MEK inhibition on the activity of T-cell checkpoint inhibitors remains incompletely understood. Here we sought to characterize the combined effects of MEK inhibition and anti-CTL...

patients and methods in this cross-sectional study, peripheral mononuclear cells (pbmcs) were isolated from peripheral blood of 29 patients with newly diagnosed pulmonary tb and 19 patients with positive tuberculin skin test. the pbmcs were activated with ppd for 72 hours. activated cells were harvested, rna was extracted and cdna was synthesized. a real-time taqman method was designed and opti...

conclusions according to the results, the polymorphisms within the +49 position of ctla-4 can be associated with vl and may be considered as risk factors for the disease. results our results indicated that both ctla-4 +49a/g polymorphisms were significantly associated with vl. materials and methods in this cross-sectional study, 88 patients with clinical presentations of vl, who were seropositi...

Rational modulation of the immune response with biologics represents one of the most promising and active areas for the realization of new therapeutic strategies. In particular, the use of function blocking monoclonal antibodies targeting checkpoint inhibitors such as CTLA-4 and PD-1 have proven to be highly effective for the systemic activation of the human immune system to treat a wide range ...

Adjuvant therapy of stage IIB/III melanoma with interferon reduces relapse and mortality by up to 33% but is accompanied by toxicity-related complications. Polymorphisms of the CTLA-4 gene associated with autoimmune diseases could help in identifying interferon treatment benefits. We previously genotyped 286 melanoma patients and 288 healthy (unrelated) individuals for six CTLA-4 polymorphisms ...

Although food allergy has emerged as a major health problem, the mechanisms that are decisive in the development of sensitization to dietary Ag remain largely unknown. CTLA-4 signaling negatively regulates immune activation, and may play a crucial role in preventing induction and/or progression of sensitization to food Ag. To elucidate the role of CTLA-4 signaling in responses to food allergens...

Pharmacodynamic biomarkers can play an important role in understanding whether a therapeutic agent has "hit its target" to impact biologic function. A pharmacodynamic biomarker for anti-CTLA-4 therapy remains to be elucidated. We previously reported that anti-CTLA-4 therapy increases the frequency of CD4 T cells expressing the inducible costimulator (ICOS) molecule. To determine whether the fre...

background: immunological factors are important in pregnancy loss because of the interaction between mother and fetus. t-regulatory cells as the component of humeral immune response play important role in the fetu-maternal interface. one of the regulatory mechanisms for these cells is mediated by antigen independent co-stimulatory signals and interaction of cytotoxic t-lymphocyte antigen 4 (b7/...

Viral persistence is associated with hierarchical antiviral CD8 T cell exhaustion with increased programmed death-1 (PD-1) expression. In HCV persistence, HCV-specific CD8 T cells from the liver (the site of viral replication) display increased PD-1 expression and a profound functional impairment that is not reversed by PD-1 blockade alone. Here, we report that the inhibitory receptor cytotoxic...

Cancer is a multifactorial disease caused by complex interactions between the genetic and environmental factors [1]. Prostate cancer (PCa) is the most common malignancy in man worldwide and its rate is increasing in both developed and developing countries [2]. The etiology of cancer is complicated and not exactly known. For this reason, recent studies have focused on the role of the immune syst...