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CD155 is an adhesion molecule belonging to the Nectin/Nectin-like family that is often overexpressed in tumor cells and involved in many different processes such as cell adhesion, migration and proliferation. It is now referred to as an immune checkpoint protein and interacts with CD96, CD226, and T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) on tumor-infiltrating lymphocytes to modulate the immune function in tumor immune microenvironment.

CD27 also known as TNFRSF7 is a member of the tumor necrosis factor receptor superfamily and plays a key role in T-cell activation by providing a costimulatory signal. Bound to its natural ligand CD70, CD27 signaling enhances T-cell proliferation and differentiation to effector and memory T cells and therefore has potential as an immune modulatory target in cancer treatment.

The CD28 surface receptor is normally expressed on CD4+ T-cells and some CD8+ T-cells to provide co-stimulatory signals required for T cell activation and survival. Its natural ligands, the B7 molecules, are found on various antigen-presenting cells. CD28 expression increases in activated T-cells. CD28 is the receptor for CD80 (B7.1) and CD86 (B7.2) proteins.

CD40 receptor and its ligand CD40L (CD154) belong to the TNF:TNFR family. CD40 is expressed on B cells, macrophages and DCs, as well as many nonimmune cells. The CD40–CD40 ligand (CD40L) system is of pivotal importance in the immune response via interactions between T cells and antigen-presenting cells. Recent data suggests that CD40 activation is critical to convert so-called cold tumors to hot ones, thus sensitizing them to checkpoint inhibition.

The CD27/CD70 costimulatory pathway is part of the TNF receptor/ligand family and regulates cellular activity in subsets of T, B and natural killer cells. CD70 is only transiently expressed on T and B cells following antigen activation and on mature dendritic cells. The interaction of CD70/CD27 is implicated in tumor cell and regulatory T cell survival.

The membrane bound NT5E (CD73) is an ecto-5′-nucleotidase (NT5E) hydrolyzing extracellular adenosine monophosphate (AMP) into adenosine and inorganic phosphate. NT5E plays a significant role as immune-inhibitory checkpoint molecule. Indeed, infiltration of tumors by NT5E expressing regulatory immune cells such as Tregs results in accumulation of immunosuppressive adenosine that can activate cAMP signaling in T cells expressing the A2A adenosine receptor (ADORA2A).

CD80 (also known as B7-1) is a costimulatory molecule known for its role in T-cell activation and also in regulating the activity of normal and malignant B cells. CD80 is the ligand for the proteins CD28 (for autoregulation and intercellular association) and CTLA-4 (for attenuation of regulation and cellular disassociation) found on the surface of T-cells. It is currently recognized as one of the most potent costimulatory molecules by which immune cells limit cancer progression.

CD96 (also known as TACTILE) is a member of the immunoglobulin superfamily that interact with nectin and nectin-like proteins. Other family members include CD226 (DNAM-1), T cell immunoglobulin and ITM domain (TIGIT). CD96 is regarded as a potent modulator of antitumor immune responses. It has been shown to negatively regulate NK cell-mediated immune surveillance and to intervene in multidimensional adhesion, inhibition, and activation of participating cells.

CTLA4 (cytotoxic T-lymphocyte-associated protein 4), also known as CD152 is a protein receptor that functions as an immune checkpoint and downregulates immune responses. Checkpoint proteins, such as B7-1/B7-2 on antigen-presenting cells and CTLA4 on T cells, help keep the body’s immune responses in check. It is constitutively expressed by Tregs but can also be upregulated by other T cell subsets, especially CD4+ T cells, upon activation.

IDO1, also known as indoleamine 2,3-dioxygenase, is an enzyme that catalyzes the rate-limiting first step in tryptophan catabolism. IDO1 is overexpressed in response to interferon gamma (IFNγ) and causes immunosuppression through breakdown of tryptophan causing inactivation of T cells.

Lymphocyte-activation gene 3 (LAG3) is a member of the immunoglobulin superfamily and a CD4 homolog. It is an immune checkpoint receptor protein found on the cell surface of effector T cells and regulatory T cells (Tregs) and functions to control T cell response, activation and growth. Accumulating evidence indicates that LAG3 is an inhibitory coreceptor and plays pivotal roles in autoimmunity, tumor immunity, and anti-infection immunity.

Programmed cell death protein 1, also known as PD-1 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.

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.

TIGIT is a emerging immune checkpoint receptor expressed on T cells and NK cells. TIGIT is a negative regulator of cytotoxic lymphocytes and has been observed up-regulated in various malignancies. Due to its broad expression on lymphocytes, TIGIT may prevent tumour antigen release by NK cells, impair T cell priming by DCs or inhibit cancer cell killing by CD8+ T cells. Inhibition of TIGIT may restore anti-tumor T cell activity through competition with its costimulatory receptor, CD226.

CD39 is a NTPDase (ecto-nucleoside triphosphate diphosphohydrolase) that regulates immune responses balance by hydrolyzing ATP and ADP. It is expressed by B cells, innate cells, regulatory T cells as well as activated CD4 and CD8 T cells, which, in coordination with several other markers such as CD73 can result in local production of adenosine leading to an immunosuppressive environment. Its expression is regarded as an immune checkpoint mediator that interferes with antitumor or anti-inflammatory immune responses.

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.

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.

CTLA4 (cytotoxic T-lymphocyte-associated protein 4), also known as CD152 is a protein receptor that functions as an immune checkpoint and downregulates immune responses. Checkpoint proteins, such as B7-1/B7-2 on antigen-presenting cells and CTLA4 on T cells, help keep the body’s immune responses in check. It is constitutively expressed by Tregs but can also be upregulated by other T cell subsets, especially CD4+ T cells, upon activation.

Lymphocyte-activation gene 3 (LAG3) is a member of the immunoglobulin superfamily and a CD4 homolog. It is an immune checkpoint receptor protein found on the cell surface of effector T cells and regulatory T cells (Tregs) and functions to control T cell response, activation and growth. Accumulating evidence indicates that LAG3 is an inhibitory coreceptor and plays pivotal roles in autoimmunity, tumor immunity, and anti-infection immunity.

Programmed cell death protein 1, also known as PD-1 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.

TIGIT is a emerging immune checkpoint receptor expressed on T cells and NK cells. TIGIT is a negative regulator of cytotoxic lymphocytes and has been observed up-regulated in various malignancies. Due to its broad expression on lymphocytes, TIGIT may prevent tumour antigen release by NK cells, impair T cell priming by DCs or inhibit cancer cell killing by CD8+ T cells. Inhibition of TIGIT may restore anti-tumor T cell activity through competition with its costimulatory receptor, CD226.

Arginase-1 is one of three enzymes that metabolise arginine: ARG1, ARG2, and inducible nitric oxide synthase (iNOS). Arginase-1 induces the breakdown of L-arginine. T cell receptors rely on L-arginine for signaling and cell proliferation. In the context of pro-tumor myeloid cells, Arginase-1 may suppress immune cell signaling and potentially suppress cytotoxic T cell activity.

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.

CD16 is also known as type III Fcγ receptor. It is involved in antibody-dependent cell-mediated cytotoxicity and is expressed on large granular lymphocytes (LGLs) of NK and T-cells. There is also lower levels of CD16 expression on granulocytes, tissue macrophages, and subsets of monocytes, eosinophils and dendritic 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.

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.

CD86 (also known as also known as B7-2)a homolog of CD80 that binds the exact same receptors is expressed on dendritic cells, Langerhans cells, macrophages, B-cells (including memory B-cells), and on other antigen-presenting cells. Along with CD80, CD86 provides costimulatory signals necessary for T cell activation and survival.

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.

In mammals, there are three different isoforms of Nitric Oxide Synthase (NOS), endothelial NOS (eNOS), neuronal NOS (nNOS) and inducible NOS (iNOS). In many tumors, iNOS expression is high and overexpression of iNOS predicts poor clinical outcomes for patients with malignant cancers, e.g., gastric, bladder, and colorectal cancers; however, other studies also reported no obvious relationship between iNOS expression and prognosis of solid tumors.

Arginase-1 is one of three enzymes that metabolise arginine: ARG1, ARG2, and inducible nitric oxide synthase (iNOS). Arginase-1 induces the breakdown of L-arginine. T cell receptors rely on L-arginine for signaling and cell proliferation. In the context of pro-tumor myeloid cells, Arginase-1 may suppress immune cell signaling and potentially suppress cytotoxic T cell activity.

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.

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.

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.

CD16 is also known as type III Fcγ receptor. It is involved in antibody-dependent cell-mediated cytotoxicity and is expressed on large granular lymphocytes (LGLs) of NK and T-cells. There is also lower levels of CD16 expression on granulocytes, tissue macrophages, and subsets of monocytes, eosinophils and dendritic cells.

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.

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.

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.

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.

Desmin filaments are mainly located at the periphery of Z-disk of striated muscles and at the dense bodies of smooth muscle cells, and they have been postulated to play a critical role in the maintenance of structural and mechanical integrity of the contractile apparatus in muscle tissues. It is highly positive in rhabdomyosarcoma

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.

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.

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.

The transcription factor T cell factor 1 (TCF1), encoded by Tcf7, is the downstream transcription factor of the canonical Wnt signaling pathway. TCF1 is important for T cell development and maturation. TCF1 appears to be an important regulator of anti-tumor immunity, as deletion of Tcf7 abolishes tumor control both in the untreated setting and upon immune checkpoint blockade.

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.

CD138 (syndecan-1) is a canonical plasma cell marker. Its many functions, include wound healing, cell adhesion and endocytosis. Importantly many proteins can bind to CD138, including extracellular matrix components and integrins for adhesion. Altered CD138 expression has been described in various malignant tumor types and poor patient prognosis.

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).

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.

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.

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.

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.

Clec10a, also known as C-type lectin domain family 10 member A. Members of this family share a common protein fold and have diverse functions, such as cell adhesion, cell-cell signaling, glycoprotein turnover, and roles in inflammation and immune response. CLEC10A recognizes and acts on tumor-associated Tn antigens and effectively presents the antigens to CD4 T cells.

Clec9a (or DNGR), a C-type lectin receptor (CLR) is a type II transmembrane protein that is selectively expressed by type 1 conventional dendritic cells. For example, the CD141+ DCs exclusively express CLEC9A, which is important for the regulation of CD8+ T cell responses. CLEC9A is a damage recognition receptor that recognizes cytoskeletal actin filaments or complexes revealed by dead or damaged cells and facilitates cross-presentation of cell associated antigens.

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.

α-Smooth muscle actin (α-SMA) is regarded as a marker for a subset of activated fibrogenic cells, myofibroblasts, important effector cells of tissue fibrogenesis. Increased expression of α-SMA has been found to be associated with shorter disease-free survival in many tumor types including lung, colorectal and pancreatic cancers.

CD299 is also known as CLEC4M, and is a type II integral membrane protein. It efficiently binds intercellular adhesion molecule 3 (ICAM3) and HIV-1 gp120 and enhances HIV-1 infection of T cells. CD299/CLEC4M is 77% identical to CD209 antigen, a HIV gp120-binding protein.

CD31, also known as platelet endothelial cell adhesion molecule 1 (PECAM-1) is a glycoprotein expressed on endothelial cells, platelets and some leukocytes. CD31 is a robust marker of endothelial differentiation. Its functions include immune cell adhesion and trans-endothelial migration, coagulation, angiogenesis, and integrin activation as well as having an important role in the regulation of proliferation and apoptosis. CD31 is also expressed on a variety of tumor cells and contributes to tumor cell invasion.

CD138 (syndecan-1) is a canonical plasma cell marker. Its many functions, include wound healing, cell adhesion and endocytosis. Importantly many proteins can bind to CD138, including extracellular matrix components and integrins for adhesion. Altered CD138 expression has been described in various malignant tumor types and poor patient prognosis.

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).

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.

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.

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.

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.

The B-cell lymphoma-2 (BCL-2) protein family participates in the regulation of many vital cellular functions but importantly as master regulators of apoptosis, tumorigenesis and cellular responses to anti-cancer therapy. BCL-2, the founding member maintains the integrity of the mitochondrial membrane, preventing cytochrome c release and its subsequent binding to apoptosis activating factor-1. BCL-2 increases the survival kinetics of the cell specifically by blocking apoptosis.

The B-cell lymphoma-2 (BCL-2) protein family participates in the regulation of many vital cellular functions but importantly as master regulators of apoptosis, tumorigenesis and cellular responses to anti-cancer therapy. The anti-apoptotic function of BCL-XL often correlates with it being overexpressed in many tumor types, e.g., CRC. Recent work reveals that targeting BCL-XL has the potential to improve cancer immunotherapy, particularly as a potential molecular target of tumor-infiltrating Tregs.

β-Catenin was initially discovered as one of the E-cadherin-associated molecules on the cell membrane and subsequent analysis revealed a critical role of Wnt proteins in activating the β-catenin signaling pathway β-Catenin is regarded as a multifunctional protein with a central role in physiological homeostasis. Its aberrant high expression leads to various diseases including cancer through its promotion of cell proliferation and survival pathways. It is a promising target for cancer prevention and therapy.

The B-cell lymphoma-2 (BCL-2) protein family participates in the regulation of many vital cellular functions but importantly as master regulators of apoptosis, tumorigenesis and cellular responses to anti-cancer therapy. BIM represents a BH3-only proapoptotic member of the BCL-2 family of apoptotic regulatory proteins. BIM expression is correlated with improved tumor survival outcome; and its, up-regulation can restore cancer cells sensitive to targeted therapies.

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.

Myeloid leukemia 1 (MCL-1) is an antiapoptotic protein of the BCL-2 family that prevents apoptosis by binding to the pro-apoptotic BCL-2. The abilities of malignant cells to evade cell death likewise depend on individual or multiple pro-survival proteins BCL-2 family members (MCL-1, BCL-2, BCL-XL) that bind to and sequester pro-apoptotic BH3-only activator as well as effector molecules.

CD27 also known as TNFRSF7 is a member of the tumor necrosis factor receptor superfamily and plays a key role in T-cell activation by providing a costimulatory signal. Bound to its natural ligand CD70, CD27 signaling enhances T-cell proliferation and differentiation to effector and memory T cells and therefore has potential as an immune modulatory target in cancer treatment.

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.

CD38 also known as cyclic ADP ribose hydrolase is a glycoprotein found on the surface of CD4+, CD8+ T cells, B lymphocytes and natural killer cells. CD38 also functions in cell adhesion, signal transduction and calcium signaling particularly its enzymatic activity which includes the production of adenosine diphosphate ribose (ADPR) or cyclic ADPR (cADPR). The functions of CD38 in the tumor microenvironment ultimately decrease extracellular NAD+, alters calcium signaling cascades, and produce immunosuppressive adenosine.

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.

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.

The CD27/CD70 costimulatory pathway is part of the TNF receptor/ligand family and regulates cellular activity in subsets of T, B and natural killer cells. CD70 is only transiently expressed on T and B cells following antigen activation and on mature dendritic cells. The interaction of CD70/CD27 is implicated in tumor cell and regulatory T cell survival.

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.

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.

Lymphocyte-activation gene 3 (LAG3) is a member of the immunoglobulin superfamily and a CD4 homolog. It is an immune checkpoint receptor protein found on the cell surface of effector T cells and regulatory T cells (Tregs) and functions to control T cell response, activation and growth. Accumulating evidence indicates that LAG3 is an inhibitory coreceptor and plays pivotal roles in autoimmunity, tumor immunity, and anti-infection immunity.

Programmed cell death protein 1, also known as PD-1 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.

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.

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).

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.

CD335, also known as NKp46, belongs to the natural cytotoxicity receptor (NCR) family and it is selectively expressed on NK cells and a subset of NKT cells. It is involved in NK cell triggering of receptors recognizing non-MHC ligands during the process of natural cytotoxicity and tumor cell lysis by NK cells.

CD38 also known as cyclic ADP ribose hydrolase is a glycoprotein found on the surface of CD4+, CD8+ T cells, B lymphocytes and natural killer cells. CD38 also functions in cell adhesion, signal transduction and calcium signaling particularly its enzymatic activity which includes the production of adenosine diphosphate ribose (ADPR) or cyclic ADPR (cADPR). The functions of CD38 in the tumor microenvironment ultimately decrease extracellular NAD+, alters calcium signaling cascades, and produce immunosuppressive adenosine.

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.

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.

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.

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.

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.

B-cell maturation antigen (BCMA), also referred to as tumor necrosis factor receptor superfamily member 17 (TNFRSF17) is a member of the tumor necrosis factor receptor superfamily and is expressed by mature B lymphocytes, plays a critical role in regulating B-cell proliferation and survival. Its overexpression and activation are associated with several hematologic malignancies, including multiple myeloma, non-Hodgkin lymphoma, and Hodgkin lymphoma.

CD138 (syndecan-1) is a canonical plasma cell marker. Its many functions, include wound healing, cell adhesion and endocytosis. Importantly many proteins can bind to CD138, including extracellular matrix components and integrins for adhesion. Altered CD138 expression has been described in various malignant tumor types and poor patient prognosis.

CD19 is also known as B-Lymphocyte Surface Antigen B4, T-Cell Surface Antigen Leu-12 and CVID3 and is expressed on follicular dendritic cells and B cells. It is critically involved in establishing intrinsic B cell signaling levels by modulating both B cell receptor (BCR)-dependent and independent signaling. It also regulates early lymphomagenesis by stabilizing the expression of the proto-oncogene c-myc.

CD22 also known as Siglec-2 is a transmembrane glycoprotein expressed by mature B cells. It inhibits signal transduction by the B cell receptor and its co-receptor CD19 as well as B cell survival, through mechanisms that are both dependent on, and independent of, its ligand-binding activity. Given that CD22 is expressed on the surface of most B-cell leukemias and lymphomas it has therefore been explored as a target for CAR and Ab-based therapies.

CD27 also known as TNFRSF7 is a member of the tumor necrosis factor receptor superfamily and plays a key role in T-cell activation by providing a costimulatory signal. Bound to its natural ligand CD70, CD27 signaling enhances T-cell proliferation and differentiation to effector and memory T cells and therefore has potential as an immune modulatory target in cancer treatment.

CD38 also known as cyclic ADP ribose hydrolase is a glycoprotein found on the surface of CD4+, CD8+ T cells, B lymphocytes and natural killer cells. CD38 also functions in cell adhesion, signal transduction and calcium signaling particularly its enzymatic activity which includes the production of adenosine diphosphate ribose (ADPR) or cyclic ADPR (cADPR). The functions of CD38 in the tumor microenvironment ultimately decrease extracellular NAD+, alters calcium signaling cascades, and produce immunosuppressive adenosine.

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.

Paired box protein Pax-5 (Pax5) are important regulators in early development, and alterations in the expression of their genes are thought to contribute to tumor development. Its expression is detectable as early as the pro–B cell stage and subsequently in all further stages of B cell development until the plasma cell stage are important regulators in early development. They have been implicated in human B cell malignancies, as it is deregulated by chromosomal translocations in a subset of acute lymphoblastic leukemias and non-Hodgkin lymphomas.