Antibodies targeting CTLA-4 have been successfully used as cancer immunotherapy. We find that the antitumor effects of CTLA-4 blockade depend on distinct Bacteroides species. In mice and patients, T cell responses specific for B. thetaiotaomicron or B. fragilis were associated with the efficacy of CTLA-4 blockade. Tumors in antibiotic-treated or germ-free mice did not respond to CTLA blockade. ...

background:  cytotoxic t lymphocyte–associated antigen 4 (ctla-4) molecules are expressed on t-cells and inhibit their function by inhibiting activation of subsequent t-cell molecular pathways. blocking of ctla-4 inhibits the growth of malignant tumor cells. anti-ctla-4 monoclonal antibodies activate the immune system against cancer. due to several advantages of single-chain antibodies (scfvs) ...

many studies have shown that cytotoxic t lymphocyte antigen-4 (ctla-4) gene variants are associated with several autoimmune diseases particularly type 1 diabetes. due to the lack of consistent data for this association with type 2 diabetes (t2d), this study explored the possible influence of ctla-4 gene polymorphisms at -1722 (t/c), -318 (c/t), and +49 (g/a) positions for susceptibility to t2d ...

background: the prevalence of hepatitis c virus (hcv) infection is increasing worldwide. cytotoxic t-lymphocyte-associated protein 4 (ctla-4) may play a role in the intensity of the disease. the aim of this study was to evaluate the association between genetic variants of the ctla-4 and hcv infection. methods: restriction fragment length polymorphism-polymerase chain reaction (rflp-pcr) was per...

We and others previously reported that cytotoxic T lymphocyte antigen-4 (CTLA-4) regulates the severity of peptide-induced experimental autoimmune encephalomyelitis (EAE) in mouse strains that are inherently susceptible to the disease. In this report, we show that CTLA-4 engagement also controls disease susceptibility in BALB/c mice, a strain considered to be resistant to EAE induction. Althoug...

CTLA-4 (CD152) is a regulatory molecule in the immune system fundamentally important for the inhibition of T cell activity that is mediated by an unknown mechanism. Here we demonstrate similarities of CTLA-4 and Itch deficient mice and that CTLA-4 deficient T cells show a massive reduction in the overall ubiquitination of proteins. CTLA-4-mediated signal transduction leads to increased de-phosp...

Cancer immunotherapy has shown promising results when combined with chemotherapy. Blocking CTLA-4 signaling by monoclonal antibody between cycles of chemotherapy may inhibit cancer cell repopulation and enhance the antitumoral immune reaction, thus improve the efficacy of chemotherapy in mesothelioma. The impact of CTLA-4 blockade on the early stage of tumor development was evaluated in a subcu...

Antibody blockade of the inhibitory CTLA-4 pathway has led to clinical benefit in a subset of patients with metastatic melanoma. Anti-CTLA-4 enhances T cell responses, including production of IFN-γ, which is a critical cytokine for host immune responses. However, the role of IFN-γ signaling in tumor cells in the setting of anti-CTLA-4 therapy remains unknown. Here, we demonstrate that patients ...

CTLA-4 is a negative regulator of T cell responses. Sequence analysis of this molecule reveals the presence of two cytoplasmic tyrosine residues at positions 165 and 182 that are potential Src homology (SH)-2 domain binding sites. The role of phosphorylation of these residues in CTLA-4-mediated signaling is unknown. Here, we show that sole TCR ligation induces zeta-associated protein (ZAP)-70-d...

T cell activation involves not only recognition of antigen presented by the MHC, but also nonspecific interactions termed "costimulation." The costimulatory molecules B7-1 and B7-2 are ligands on antigen-presenting cells for the CD28 and CTLA-4 receptors on T cells. Previously, a fusion protein consisting of human CTLA-4 linked to human Fc was shown to bind B7-1 and B7-2 with high avidity and t...