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Tumor-associated Macrophage
Tumor-associated macrophages (TAMs) are a class of immune cells present in high numbers in the microenvironment of solid tumors. They are heavily involved in cancer-related inflammation. Macrophages are known to originate from bone marrow-derived blood monocytes (monocyte-derived macrophages) or yolk sac progenitors (tissue-resident macrophages), but the exact origin of TAMs in human tumors remains to be elucidated. The composition of monocyte-derived macrophages and tissue-resident macrophages in the tumor microenvironment depends on the tumor type, stage, size, and location, thus it has been proposed that TAM identity and heterogeneity is the outcome of interactions between tumor-derived, tissue-specific, and developmental signals. Function Although there is some debate, most evidence suggests that TAMs have a tumor-promoting phenotype. TAMs affect most aspects of tumor cell biology and drive pathological phenomena including tumor cell proliferation, tumor angiogenesis, invasion ...
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Metastasis
Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, are metastases (mets). It is generally distinguished from cancer invasion, which is the direct extension and penetration by cancer cells into neighboring tissues. Cancer occurs after cells are genetically altered to proliferate rapidly and indefinitely. This uncontrolled proliferation by mitosis produces a primary heterogeneic tumour. The cells which constitute the tumor eventually undergo metaplasia, followed by dysplasia then anaplasia, resulting in a malignant phenotype. This malignancy allows for invasion into the circulation, followed by invasion to a second site for tumorigenesis. Some cancer cells known as circulating tumor cells acquire the ability to penetrate the walls of lymphatic or blood vessels, after which they are ...
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CSF1
The colony stimulating factor 1 (CSF1), also known as macrophage colony-stimulating factor (M-CSF), is a secreted cytokine which causes hematopoietic stem cells to differentiate into macrophages or other related cell types. Eukaryotic cells also produce M-CSF in order to combat intercellular viral infection. It is one of the three experimentally described colony-stimulating factors. M-CSF binds to the colony stimulating factor 1 receptor. It may also be involved in development of the placenta. Structure M-CSF is a cytokine, being a smaller protein involved in cell signaling. The active form of the protein is found extracellularly as a disulfide-linked homodimer, and is thought to be produced by proteolytic cleavage of membrane-bound precursors. Four transcript variants encoding three different isoforms (a proteoglycan, glycoprotein and cell surface protein) have been found for this gene. Function M-CSF (or CSF-1) is a hematopoietic growth factor that is involved in the prol ...
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Breast Cancer
Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a red or scaly patch of skin. In those with distant spread of the disease, there may be bone pain, swollen lymph nodes, shortness of breath, or yellow skin. Risk factors for developing breast cancer include obesity, a lack of physical exercise, alcoholism, hormone replacement therapy during menopause, ionizing radiation, an early age at first menstruation, having children late in life or not at all, older age, having a prior history of breast cancer, and a family history of breast cancer. About 5–10% of cases are the result of a genetic predisposition inherited from a person's parents, including BRCA1 and BRCA2 among others. Breast cancer most commonly develops in cells from the lining of milk ducts and the lobules that supply ...
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Prognosis
Prognosis ( Greek: πρόγνωσις "fore-knowing, foreseeing") is a medical term for predicting the likely or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) or remain stable over time; expectations of quality of life, such as the ability to carry out daily activities; the potential for complications and associated health issues; and the likelihood of survival (including life expectancy). A prognosis is made on the basis of the normal course of the diagnosed disease, the individual's physical and mental condition, the available treatments, and additional factors. A complete prognosis includes the expected duration, function, and description of the course of the disease, such as progressive decline, intermittent crisis, or sudden, unpredictable crisis. When applied to large statistical populations, prognostic estimates can be very accurate: for example the statement "45% of patients with severe septic shoc ...
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Macrophage Polarization
Macrophage polarization is a process by which macrophages adopt different functional programs in response to the signals from their microenvironment. This ability is connected to their multiple roles in the organism: they are powerful effector cells of the innate immune system, but also important in removal of cellular debris, embryonic development and tissue repair. By simplified classification, macrophage phenotype has been divided into 2 groups: M1 (classically activated macrophages) and M2 (alternatively activated macrophages). This broad classification was based on ''in vitro'' studies, in which cultured macrophages were treated with molecules that stimulated their phenotype switching to a particular state. In addition to chemical stimulation, it has been shown that the stiffness of the underlying substrate a macrophage is grown on can direct polarization state, functional roles and migration mode. A continuum of M1-M2 polarization may arise even in the absence of polarizing cyt ...
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Interleukin 4
The interleukin 4 (IL4, IL-4) is a cytokine that induces differentiation of naive helper T cells ( Th0 cells) to Th2 cells. Upon activation by IL-4, Th2 cells subsequently produce additional IL-4 in a positive feedback loop. IL-4 is produced primarily by mast cells, Th2 cells, eosinophils and basophils. It is closely related and has functions similar to IL-13. Function Interleukin 4 has many biological roles, including the stimulation of activated B cell and T cell proliferation, and the differentiation of B cells into plasma cells. It is a key regulator in humoral and adaptive immunity. IL-4 induces B cell class switching to IgE, and up-regulates MHC class II production. IL-4 decreases the production of Th1 cells, macrophages, IFNγ, and dendritic cells IL-12. Overproduction of IL-4 is associated with allergies. * Inflammation and wound repair Tissue macrophages play an important role in chronic inflammation and wound repair. ...
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Interferon Gamma
Interferon gamma (IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. Wheelock as a product of human leukocytes stimulated with phytohemagglutinin, and by others as a product of antigen-stimulated lymphocytes. It was also shown to be produced in human lymphocytes. or tuberculin-sensitized mouse peritoneal lymphocytes challenged with Mantoux test (PPD); the resulting supernatants were shown to inhibit growth of vesicular stomatitis virus. Those reports also contained the basic observation underlying the now widely employed IFN-γ release assay used to test for tuberculosis. In humans, the IFN-γ protein is encoded by the ''IFNG'' gene. Through cell signaling, IFN-γ plays a role in regulating the immune response of its target cell. A key signaling pathway that is activated by type II IFN is the JAK-STAT ...
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CTLA-4
CTLA-4 or CTLA4 (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. CTLA-4 is constitutively expressed in regulatory T cells but only upregulated in conventional T cells after activation – a phenomenon which is particularly notable in cancers. It acts as an "off" switch when bound to CD80 or CD86 on the surface of antigen-presenting cells. The CTLA-4 protein is encoded by the ''Ctla-4'' gene in mice and the ''CTLA-4'' gene in humans. History CTLA-4 was first identified in 1991 as a second receptor for the T cell costimulation ligand B7. In November 1995, the labs of Tak Wah Mak and Arlene H. Sharpe independently published their findings on the discovery of the function of CTLA-4 as a negative regulator of T-cell activation, by knocking out the gene in mice. Previous studies from several labs had used methods which could n ...
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Programmed Cell Death Protein 1
Programmed cell death protein 1, also known as PD-1 and CD279 (cluster of differentiation 279), is a protein on the surface of T and B cells that has a role in regulating the immune system's response to the cells of the human body by down-regulating the immune system and promoting self-tolerance by suppressing T cell inflammatory activity. This prevents autoimmune diseases, but it can also prevent the immune system from killing cancer cells. PD-1 is an immune checkpoint and guards against autoimmunity through two mechanisms. First, it promotes apoptosis (programmed cell death) of antigen-specific T-cells in lymph nodes. Second, it reduces apoptosis in regulatory T cells (anti-inflammatory, suppressive T cells). PD-1 inhibitors, a new class of drugs that block PD-1, activate the immune system to attack tumors and are used to treat certain types of cancer. The PD-1 protein in humans is encoded by the ''PDCD1'' gene. PD-1 is a cell surface receptor that belongs to the immunoglob ...
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PD-L1
Programmed death-ligand 1 (PD-L1) also known as cluster of differentiation 274 (CD274) or B7 homolog 1 (B7-H1) is a protein that in humans is encoded by the ''CD274'' gene. Programmed death-ligand 1 (PD-L1) is a 40kDa type 1 transmembrane protein that has been speculated to play a major role in suppressing the adaptive arm of immune systems during particular events such as pregnancy, tissue allografts, autoimmune disease and other disease states such as hepatitis. Normally the adaptive immune system reacts to antigens that are associated with immune system activation by exogenous or endogenous danger signals. In turn, clonal expansion of antigen-specific CD8+ T cells and/or CD4+ helper cells is propagated. The binding of PD-L1 to the inhibitory checkpoint molecule PD-1 transmits an inhibitory signal based on interaction with phosphatases ( SHP-1 or SHP-2) via Immunoreceptor Tyrosine-Based Switch Motif (ITSM). This reduces the proliferation of antigen-specific T-cells in lym ...
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Transforming Growth Factor β
Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other signaling proteins. TGFB proteins are produced by all white blood cell lineages. Activated TGF-β complexes with other factors to form a serine/threonine kinase complex that binds to TGF-β receptors. TGF-β receptors are composed of both type 1 and type 2 receptor subunits. After the binding of TGF-β, the type 2 receptor kinase phosphorylates and activates the type 1 receptor kinase that activates a signaling cascade. This leads to the activation of different downstream substrates and regulatory proteins, inducing transcription of different target genes that function in differentiation, chemotaxis, proliferation, and activation of many immune cells. TGF-β is secreted by many cell types, including macrophages, in a latent form in which it ...
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