What does CTLA-4 do?
CTLA-4 is a molecule expressed on T cells after activation and strongly binds to co-stimulatory molecules on antigen-presenting cells that prevent binding of these molecules needed for T-cell activation. The CTLA-4 molecule acts as a halting mechanism, decreasing the function of T cells.
Does CTLA-4 have Itim?
CTLA-4 has a 36-amino acid cytoplasmic tail that is devoid of intrinsic enzymatic activity and lacks a bona fide ITIM motif [8]. Unlike CD28, which is a surface receptor, CTLA-4 is highly endocytic, spending much of its time in intracellular vesicles (Box 1).
Is CTLA-4 an immune checkpoint?
CTLA4 or CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), also known as CD152 (cluster of differentiation 152), is a protein receptor that functions as an immune checkpoint and downregulates immune responses.
Do cancer cells express CTLA-4?
CTLA-4 is constitutively expressed on tumor cells and can trigger apoptosis upon ligand interaction. Int J Cancer.
Is ipilimumab chemotherapy or immunotherapy?
Ipilimumab is an anti-CTLA-4 inhibitor, which is: A type of immunotherapy known as a checkpoint inhibitor, which helps your own immune system attack cancer cells.
Is ipilimumab cytotoxic?
Ipilimumab is an anti-cytotoxic T-lymphocyte antigen-4 monoclonal antibody commonly used for treatment of melanoma.
Is CTLA-4 a cytokine?
Inflammatory cytokines are sufficient to trigger CTLA-4 expression on the MAIT cell surface. CTLA-4 protein is expressed by conventional T cells following TCR stimulation and constitutively expressed by Treg (31, 32).
How does an anti CTLA-4 antibody promote cancer immunity?
Antibodies to human CTLA-4 have been shown to induce long-lasting protection against melanoma. It is assumed that these antibodies cause tumor rejection by blocking negative signaling from the B7-CTLA-4 interactions to enhance priming of naïve T cells in the lymphoid organs.
How does binding of a CTLA-4 inhibitor restore the anti tumor immune response?
The exact mechanism by which anti-CTLA-4 antibodies induce an antitumor response is unclear, although research to date suggests that CTLA-4 blockade affects the immune priming phase by supporting the activation and proliferation of a higher number of effector T cells, regardless of TCR specificity, and by reducing Treg …
How often is ipilimumab given?
Ipilimumab is now approved worldwide and is one of the most common drugs used as front-line treatment for metastatic melanoma. The approved dose and schedule for ipilimumab is 3 mg/kg infused over 90 minutes administered every 3 weeks for up to four doses.
How is CTLA-4 used in immunohistochemistry?
Our findings show that CTLA-4 IHC can be used to reliably label lymphocytes in FFPE human tissues, making it possible to investigate the role of CTLA-4 in the tumor microenvironment. Keywords: CTLA-4; FoxP3; cancer; image analysis; immuno-oncology; immunohistochemistry.
How is CTLA-4 used in cancer profiling?
CTLA-4 Immunohistochemistry and Quantitative Image Analysis for Profiling of Human Cancers There is an important need in immuno-oncology to develop reliable immunohistochemistry (IHC) to assess the expression of CTLA-4+ tumor-infiltrating lymphocytes in human cancers and quantify them with image analysis (IA).
Where are CTLA-4 + and FOXP3 + lymphocytes located?
The CTLA-4/FoxP3 (forkhead box P3 protein) duplex IHC demonstrated that CTLA-4+/FoxP3-lymphocytes predominated in the germinal centers of SLOs and tumor tertiary lymphoid structures (TLSs), whereas CTLA-4+/FoxP3+lymphocytes populated the T-cell zone of SLOs and TLSs, plus tumor stroma.
What kind of disease is caused by CTLA4?
Genetic variation in CTLA4 influences susceptibility to systemic lupus erythematosus (SLE) [MIM:152700]. SLE is a chronic, inflammatory and often febrile multisystemic disorder of connective tissue. It affects principally the skin, joints, kidneys and serosal membranes.