Glypican-3/GPC3 is a member of the glypican family. It belongs to the glypican family and is highly expressed in lung, liver, and kidney. It is a heparan sulfate proteoglycan, which is overexpressed in various neoplasms such as hepatocellular carcinoma, malignant melanoma, and testicular yolk sac tumor, and plays an important role in cell growth and differentiation. GPC3 function is tissue dependent. In some tissues, GPC3 acts as a tumor suppressor gene, whereas in others, it acts as an oncofetal protein. GPC3 is a reliable marker for hepatocellular carcinoma. The sensitivity and specificity exceeds both alpha-fetoprotein and hepatocyte-paraffin1. GPC3 immunohistochemistry can aid in the differentiation of testicular germ cell tumors, being expressed in all yolk sac tumors but not in seminomas. GPC3 expression has also been identified in some squamous cell carcinomas of the lung and clear cell carcinomas of the ovary. Glypican-3 is currently regarded as a tumor marker and potential target for immunotherapy.
Herpesvirus entry mediator (HVEM) is a type I membrane protein in the TNF receptor superfamily, and it can both promote and inhibit T cell activity. HVEM is highly expressed on naïve CD4+ T cells, CD8+ T memory cells, regulatory T cells, dendritic cells, monocytes, and neutrophils. It functions as a receptor for BTLA, CD160, LIGHT/TNFSF14, and Lymphotoxin-alpha. Ligation of HVEM by LIGHT triggers T cell, monocyte, and neutrophil activation and contributes to Th1 inflammation and cardiac allograft rejection. In contrast, HVEM binding to CD160 or BTLA suppresses T cell and dendritic cell activation and dampens intestinal inflammation. HVEM enhances the development of CD8+ T cell memory and Treg function. It is additionally expressed on intestinal epithelial cells, where its binding by intraepithelial lymphocyte (IEL) expressed CD160 promotes epitheilal integrity and host defense. The herpesvirus envelope glycoprotein gD, which binds HVEM to initiate membrane fusion, can antagonize both BTLA and LIGHT binding.
Inducible T-cell costimulator, also known as activation-inducible lymphocyte immunomediatory molecule, CD278, AILIM, CVID1 and ICOS, belongs to the CD28 and CTLA4 cell surface receptor family.. ICOS contains one Ig-like V-type domain and exsits as a homodimer with disulfide-linked. ICOS is highly expressed on tonsillar T-cellsand can be induced by PMA and ionomycin, ICOS plays an important role in cell-cell signaling, immune responses, and regulation of cell proliferation. Defects in ICOS are the cause of immunodeficiency common variable type 1, which is a primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antige.
Interferon-alpha/beta receptor 1 (IFN-alpha / beta R1), also known as IFNAR1, are present in all tissues and even on the surface of most IFN-resistant cells. Isoform 1, isoform 2 and isoform 3 are expressed in the IFN-alpha sensitive myeloma cell line U266B1. Isoform 2 and isoform 3 are expressed in the IFN-alpha resistant myeloma cell line U266R. Isoform 1 is not expressed in IFN-alpha resistant myeloma cell line U266R. It interacts with STAT1 and STAT2, the interaction requires its phosphorylation at Tyr-466. It also interacts with FBXW11, the substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex.
Interleukin-33 (IL-33) belongs to the IL-1 superfamily. IL33 is highly expressed in endothelial venules found in tonsils, Peyer patches and mesenteric lymph nodes, but almost undetectable in placenta. IL33 induces the production of T helper-2 (Th2)-associated cytokines. IL-33 is a cytokine that mediates its biological effects by binding to and signals through IL1RL1/ST2 and IL-1 Receptor Accessory Protein (IL1RAP), activating intracellular molecules in the NF-κB and MAP kinase signaling pathways that drive production of type 2 cytokines from polarized Th2 cells.
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