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CD4 is a member of the immunoglobulin superfamily and is part of the TCR/CD3 complex, binding to MHC class II molecules and participating in signal transduction through recruitment of tyrosine kinase Lck. CD4 expression is used to identify helper T cells of which there are many different subsets including Th1, Th2, Th9, Th17, regulatory T cell, and follicular helper T cell. Each of these contributes to immune function through their unique cytokine profile.

Programmed cell death ligand 1 (PD-L1) is a type 1 transmembrane protein (B7-H1) that belongs to the B7 ligands family and may be expressed on both, hematopoietic cells (dendritic cells, macrophages, mast cells, T cells and B cells) and non-hematopoietic cells, including endothelial, epithelial and tumor cells. It plays an immunosuppressive role by inhibiting T-cell activity. Overexpression of PD-L1 by cancer cells may enable them to evade the host immune response, conferring a growth advantage to such tumors.

CD11c is one of four β2 integrins along with CD11a, CD11b and CD11d. CD11c, also known as integrin alpha X, is the most widely used defining marker for dendritic cells (DCs). It is a receptor for fibrinogen and functions in chemotaxis and cell adhesion. Integrins mediate myeloid cell recruitment from the blood vessels into tissue and lymph nodes and contribute to the immunological synapse between T cells and antigen presenting cells.

CD56, also known as neural cell adhesion molecule (NCAM) is a transmembrane glycoprotein often considered a marker of neural lineage commitment due to its discovery site. CD56 expression is most strongly associated with natural killer (NK) cells but it has also been detected on other lymphoid cells, including gamma delta (γδ), T cells and activated CD8+ T cells, as well as dendritic cells.

Sox10 (Sry-related HMg-Box gene 10) is a nuclear transcription factor invovled in differentiation of neural crest progenator cells to melanocytes and maintanace of Schwann cells. Its high expression is observed in the melanocytic tumors of skin, soft tissue and primary as well as metastatic melanoma.

CD11b is an integrin alpha M chain protein and is expressed by myeloid derived cells. It plays a key role in adherence of leukocytes to stimulate endothelium and mediates uptake of the complementcoated particles. Recent studies identify CD11b as a negative regulator of immune suppression and a target for cancer immune therapy.

CD3 is a multimeric protein composed of 4 subunits (γ, δ, ε, ζ), which are part of the T-cell receptor (TCR). Engagement of CD3 induces downstream signaling events that result in T-cell activation. The specificity of the CD3 antigen for T cells and its appearance at all stages of T cell development makes it an ideal T cell marker for both the detection of normal T cells and T cell neoplasms.

CD68 is expressed on human macrophages and other mononuclear phagocytes. CD68 is a heavily glycosylated glycoprotein that is involved in ligand binding and is a member of the scavenger receptor family. CD68 functions in phagocytic activities and macrophage homing. An increased CD68+ macrophage index is associated with metastasis, shorter disease-free interval, poor prognosis, and reduced overall survival in multiple types of cancer.

CD15 is a cluster of cell surface glycoproteins and glycolipids, also known as 3-fucosyl-N-acetyl-lactosamine or Lewis X. CD15 is a carbohydrate adhesion molecule that functions in cell-to-cell recognition processes. It is a distinguishing marker for human myeloid cells and mediates neutrophil adhesion to dendritic cells. Several studies have shown that CD15 expression is associated with prognosis and survival in a variety of cancers, such as breast cancer and Hodgkin’s lymphoma.

CD14 is a pattern recognition receptor that detects the pathogen-associate molecular patterns found on the surface of microorganisms. It is a co-receptor located on the cell surface that mediates the innate immune response.

Cytokeratins play a cytoskeletal role in epithelial tissue and are an important component of intermediate filaments. These provide a structural framework for the cell and help resist mechanical stress. The mixture of AE1 and AE3 clones are able to detect a mixture of low and high molecular weight cytokeratins, thus identifying a broad range of cytokeratins. This marker can be used to identify the epithelial nature of tissue and tumors.

Ki67 is a nuclear marker associated with cellular proliferation. Ki67 is present within the nucleus of cells undergoing division during interphase but is absent in quiescent cells. Ki67 can also be used as a prognostic indicator in certain cancers.

CD45RO is expressed on activated and memory T cells, some B cell subsets, activated monocytes/macrophages, and granulocytes. Lack of CD45RO on T cells indicates naive T cell subsets while CD45RO expression indicated previous antigen exposure and defines the memory T cell subset. High density of CD45RO+ T cells in solid tumors is associated with a better prognosis.

CD163 is a type I transmembrane protein belonging to the group B of the scavenger receptor cysteine-rich superfamily. It is involved in the clearance and endocytosis of haptoglobin-hemoglobin complexes and has been widely used to identify M2 type macrophage. The scavenging role of CD163 is critical to its anti-inflammatory response, and recent findings have shown the significance of CD163-positive macrophages in tumor progression.

CD8 is primarily expressed on cytotoxic T cells, but it can also be expressed on cortical thymocytes, dendritic cells and NK cells. CD8 is a transmembrane glycoprotein that is a co-receptor for the T cell receptor (TCR). CD8 binds MHC Class I to aid in antigen recognition and TCR-mediated activation. CD8 forms dimers of CD8ɑ and CD8β and clone C8/144B recognizes the alpha form of CD8.

FoxP3, or Forkhead Box P3 is a transcription factor important in the development and inhibitory function of regulatory T cells (Tregs). FoxP3 functions by inhibiting cytokine production and T cell effector function, thus playing a crucial role in maintenance of immunological tolerance and control of immune responses against tumors and pathogens.

Human leukocyte antigen (HLA) complex encodes the major histocompatibility complex (MHC). HLA-DR is the main isotype of 3 isotype (-DR, -DP, -DQ) responsible for presentation of antigens to T cells and B cells. Often, HLA-DR is used as a marker indicating the presence of antigen-presenting cells. HLA-DR expression in tumors has been shown to be positively associated with patient prognosis in some cancers such as colorectal cancer but is negatively associated with prognosis in other cancer types, such as glioma.

Major Histocompability Complex II (MHC II) molecules are heterodimer complex that presents peptide antigen on the surface of the professional antigen presenting cells (APC’s) like macrophages and dendritic cells. Presentation of the antigen by MHC II complex is critical in CD4 activation and development of adaptive immune response. Along with APC’s, B cells and epithelial cells also present the MHC II molecule.

CD20 is a B cell differentiation antigen expressed in B cell development from early pre-B cell stage to mature B cell stage but lost on differentiation into plasma cells. Its role is in regulating B- cell activation, proliferation and differentiation. Aberrant CD20 expression has been described in mainly B cell tumor types such as Burkitt lymphoma, non-Hodgkin lymphoma, and chronic lymphocytic leukemia (CLL).

Programmed cell death protein 1, also known as PD1 and CD279, is an inhibitory receptor expressed by all T cells during activation. It regulates T cell effector functions during physiological responses, including acute and chronic infection, cancer, and autoimmunity. When PD-1 is bound to his ligand PD-L1, it prevents T cells from killing target cells including cancer cells.

CD206 is a C-type lectin that can be found on certain populations of macrophages and dendritic cells. Also known as mannose receptor C type 1 (MRC1), it is normally expressed on M2 macrophages. CD206 is thought to play a role in innate and adaptive immunity by acting as a pattern recognition receptor for various pathogens.

Granzyme B (GrzB) is a serine protease stored in secretory granules of Cytotoxic T lymphocytes (CTLs) and Natural killer (NK) cells. Activated cytotoxic cells release granzyme B which enters the target cells where it can interact with cellular substrates to initiate cell death.