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Although many human cancers such as melanoma express tumor antigens recognized by T cells, host immune responses often fail to control tumor growth for as yet unexplained reasons. Here, we found a strong association between melanocyte expression of B7-H1 (PD-L1), an immune-inhibitory molecule, and the presence of tumor-infiltrating lymphocytes (TILs) in(More)
PURPOSE Immunomodulatory drugs differ in mechanism-of-action from directly cytotoxic cancer therapies. Identifying factors predicting clinical response could guide patient selection and therapeutic optimization. EXPERIMENTAL DESIGN Patients (N = 41) with melanoma, non-small cell lung carcinoma (NSCLC), renal cell carcinoma (RCC), colorectal carcinoma, or(More)
Decoy lymphotoxin beta receptor (LTbetaR) has potent immune inhibitory activities and thus represents a promising biologic for the treatment of inflammation, autoimmune diseases, and graft-versus-host disease (GVHD). As this reagent interrupts multiple molecular interactions, including LTbeta-LTbetaR and LIGHT-HVEM/LTbetaR, underlying molecular mechanisms(More)
PURPOSE Results from the first-in-human phase I trial of the anti-programmed death-1 (PD-1) antibody BMS-936558 in patients with treatment-refractory solid tumors, including safety, tolerability, pharmacodynamics, and immunologic correlates, have been previously reported. Here, we provide long-term follow-up on three patients from that trial who sustained(More)
Alterations in EGFR, KRAS, and ALK are oncogenic drivers in lung cancer, but how oncogenic signaling influences immunity in the tumor microenvironment is just beginning to be understood. Immunosuppression likely contributes to lung cancer, because drugs that inhibit immune checkpoints like PD-1 and PD-L1 have clinical benefit. Here, we show that activation(More)
CD28 and CTLA-4 are cell surface cosignaling molecules essential for the control of T cell activation upon the engagement of their ligands B7-1 and B7-2 from antigen-presenting cells. By employing a receptor array assay, we have demonstrated that B7-H2, best known as the ligand of inducible costimulator, was a ligand for CD28 and CTLA-4 in human, whereas(More)
Upon interaction with B7 homolog 1, programmed death-1 (PD-1) transmits a critical coinhibitory signal to T cells to negatively regulate immune responses. By extensively searching the genomic database with the IgV region of PD-1, we identified a homolog and named it PD-1 homolog (PD-1H). PD-1H is broadly expressed on the cell surface of hematopoietic cells(More)
The pure methods in a program are those that exhibit functional or side effect free behaviour, a useful property in many contexts. However, existing purity investigations present primarily staticresults. We perform a detailed examination of dynamic method purityin Java programs using a JVM-based analysis. We evaluate multiple purity definitions that range(More)
B7-H4 is an immunoglobulin superfamily molecule and shown to be inhibitory for T-cell responses. To explore physiologic roles of B7-H4, we created B7-H4-deficient (KO) mice by genetic targeting. B7-H4KO mice are healthy and their T- and B-cell responses to polyclonal antigens are in normal range. However, B7-H4KO mice are more resistant to infection by(More)
BACKGROUND The role of common polymorphisms of the estrogen receptor-1 in coronary artery disease (CAD) and it association with angiographic severity reminds conflicting in sexes and different races. METHODS Two-hundred ten angiographically defined Chinese CAD patients and 174 control subjects were enrolled. DNA was obtained and the polymorphisms were(More)