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Macrophages are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris, and foreign substances, which do not have proteins that are specific to healthy body cells on their surface. This process is called phagocytosis, which acts to defend the host against infection and injury.
Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system. They belong to the rapidly expanding family of known innate lymphoid cells (ILC) and represent 5–20% of all circulating lymphocytes in humans. The role of NK cells is analogous to that of cytotoxic T cells in the vertebrate adaptive immune response. NK cells provide rapid responses to virus-infected cell and other intracellular pathogens acting at around 3 days after infection, and respond to tumor formation. Most immune cells detect the antigen presented on major histocompatibility complex (MHC) on infected cell surfaces, but NK cells can recognize and kill stressed cells in the absence of antibodies and MHC, allowing for a much faster immune reaction. They were named "natural killers" because of the notion that they do not require activation to kill cells that are missing "self" markers of MHC class I. This role is especially important because harmful cells that are missing MHC I markers cannot be detected and destroyed by other immune cells, such as T lymphocyte cells.
A biopsy is a medical test commonly performed by a surgeon, an interventional radiologist, or an interventional cardiologist. The process involves the extraction of sample cells or tissues for examination to determine the presence or extent of a disease. The tissue is then fixed, dehydrated, embedded, sectioned, stained and mounted before it is generally examined under a microscope by a pathologist; it may also be analyzed chemically. When an entire lump or suspicious area is removed, the procedure is called an excisional biopsy. An incisional biopsy or core biopsy samples a portion of the abnormal tissue without attempting to remove the entire lesion or tumor. When a sample of tissue or fluid is removed with a needle in such a way that cells are removed without preserving the histological architecture of the tissue cells, the procedure is called a needle aspiration biopsy. Biopsies are most commonly performed for insight into possible cancerous or inflammatory conditions.
Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and monocyte-derived dendritic cells. As a part of the vertebrate innate immune system monocytes also influence adaptive immune responses and exert tissue repair functions. There are at least three subclasses of monocytes in human blood based on their phenotypic receptors.
An antigen-presenting cell (APC) or accessory cell is a cell that displays antigen bound by major histocompatibility complex (MHC) proteins on its surface; this process is known as antigen presentation. T cells may recognize these complexes using their T cell receptors (TCRs). APCs process antigens and present them to T-cells.
CD14 is a human protein made mostly by macrophages as part of the innate immune system. It helps to detect bacteria in the body by binding lipopolysaccharide (LPS), a pathogen-associated molecular pattern (PAMP).
In medicine, a biomarker is a measurable indicator of the severity or presence of some disease state. It may be defined as a "cellular, biochemical or molecular alteration in cells, tissues or fluids that can be measured and evaluated to indicate normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention." More generally a biomarker is anything that can be used as an indicator of a particular disease state or some other physiological state of an organism. According to the WHO, the indicator may be chemical, physical, or biological in nature - and the measurement may be functional, physiological, biochemical, cellular, or molecular.
Monoblasts are the committed progenitor cells that differentiated from a committed macrophage or dendritic cell precursor (MDP) in the process of hematopoiesis. They are the first developmental stage in the monocyte series leading to a macrophage. Their myeloid cell fate is induced by the concentration of cytokines they are surrounded by during development. These cytokines induce the activation of transcription factors which push completion of the monoblast's myeloid cell fate. Monoblasts are normally found in bone marrow and do not appear in the normal peripheral blood. They mature into monocytes which, in turn, develop into macrophages. They then are seen as macrophages in the normal peripheral blood and many different tissues of the body. Macrophages can produce a variety of effector molecules that initiate local, systemic inflammatory responses. These monoblast differentiated cells are equipped to fight off foreign invaders using pattern recognition receptors to detect antigen as part of the innate immune response.
Chemokine ligand 8 (CCL8), also known as monocyte chemoattractant protein 2 (MCP2), is a protein that in humans is encoded by the CCL8 gene.
CD16, also known as FcγRIII, is a cluster of differentiation molecule found on the surface of natural killer cells, neutrophils, monocytes, macrophages, and certain T cells. CD16 has been identified as Fc receptors FcγRIIIa (CD16a) and FcγRIIIb (CD16b), which participate in signal transduction. The most well-researched membrane receptor implicated in triggering lysis by NK cells, CD16 is a molecule of the immunoglobulin superfamily (IgSF) involved in antibody-dependent cellular cytotoxicity (ADCC). It can be used to isolate populations of specific immune cells through fluorescent-activated cell sorting (FACS) or magnetic-activated cell sorting, using antibodies directed towards CD16.
Deoxyribonuclease-1-like 1 is an enzyme that in humans is encoded by the DNASE1L1 gene. It is also known as DNaseX due to its localisation on the X chromosome.
Transketolase-like-1 (TKTL1) is a gene closely related to the transketolase gene (TKT). It emerged in mammals during the course of evolution and, according to the latest research findings, is considered one of the key genes that distinguishes modern humans from Neanderthals.
A circulating tumor cell (CTC) is a cell that has shed into the vasculature or lymphatics from a primary tumor and is carried around the body in the blood circulation. CTCs can extravasate and become seeds for the subsequent growth of additional tumors (metastases) in distant organs, a mechanism that is responsible for the vast majority of cancer-related deaths. The detection and analysis of CTCs can assist early patient prognoses and determine appropriate tailored treatments. Currently, there is one FDA-approved method for CTC detection, CellSearch, which is used to diagnose breast, colorectal and prostate cancer.
M30 Apoptosense® ELISA is an enzyme-linked immunosorbent assay developed for the detection of soluble caspase-cleaved keratin 18.
Urelumab is a fully human, non‐ligand binding, CD137 agonist immunoglobulin‐γ 4 (IgG4) monoclonal antibody. It was developed utilizing Medarex's UltiMAb(R) technology by Bristol-Myers Squibb for the treatment of cancer and solid tumors. Urelumab promotes anti-tumor immunity, or an immune response against tumor cells, via CD137 activation. The application of Urelumab has been limited due to the fact that it can cause severe liver toxicity.
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 or yolk sac progenitors, 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.
Circulating tumor DNA (ctDNA) is tumor-derived fragmented DNA in the bloodstream that is not associated with cells. ctDNA should not be confused with cell-free DNA (cfDNA), a broader term which describes DNA that is freely circulating in the bloodstream, but is not necessarily of tumor origin. Because ctDNA may reflect the entire tumor genome, it has gained traction for its potential clinical utility; "liquid biopsies" in the form of blood draws may be taken at various time points to monitor tumor progression throughout the treatment regimen.
A liquid biopsy, also known as fluid biopsy or fluid phase biopsy, is the sampling and analysis of non-solid biological tissue, primarily blood. Like traditional biopsy, this type of technique is mainly used as a diagnostic and monitoring tool for diseases such as cancer, with the added benefit of being largely non-invasive. Liquid biopsies may also be used to validate the efficiency of a cancer treatment drug by taking multiple samples in the span of a few weeks. The technology may also prove beneficial for patients after treatment to monitor relapse.
Circulating free DNA (cfDNA) (also known as cell-free DNA) are degraded DNA fragments released to body fluids such as blood plasma, urine, cerebrospinal fluid, etc. Typical sizes of cfDNA fragments reflect chromatosome particles (~165bp), as well as multiples of nucleosomes, which protect DNA from digestion by apoptotic nucleases. The term cfDNA can be used to describe various forms of DNA freely circulating in body fluids, including circulating tumor DNA (ctDNA), cell-free mitochondrial DNA (ccf mtDNA), cell-free fetal DNA (cffDNA) and donor-derived cell-free DNA (dd-cfDNA). Elevated levels of cfDNA are observed in cancer, especially in advanced disease. There is evidence that cfDNA becomes increasingly frequent in circulation with the onset of age. cfDNA has been shown to be a useful biomarker for a multitude of ailments other than cancer and fetal medicine. This includes but is not limited to trauma, sepsis, aseptic inflammation, myocardial infarction, stroke, transplantation, diabetes, and sickle cell disease. cfDNA is mostly a double-stranded extracellular molecule of DNA, consisting of small fragments (50 to 200 bp) and larger fragments (21 kb) and has been recognized as an accurate marker for the diagnosis of prostate cancer and breast cancer.
Focused-ultrasound-mediated diagnostics or FUS-mediated diagnostics are an area of clinical diagnostic tools that use ultrasound to detect diseases and cancers. Although ultrasound has been used for imaging in various settings, focused-ultrasound refers to the detection of specific cells and biomarkers under flow combining ultrasound with lasers, microbubbles, and imaging techniques. Current diagnostic techniques for detecting tumors and diseases using biopsies often include invasive procedures and require improved accuracy, especially in cases such as glioblastoma and melanoma. The field of FUS-mediated diagnostics targeting cells and biomarkers is being investigated for overcoming these limitations.
References
- ↑ Grimm, Martin; Schmitt, Steffen; Teriete, Peter; Biegner, Thorsten; Stenzl, Arnulf; Hennenlotter, Jörg; Muhs, Hans-Joachim; Munz, Adelheid; Nadtotschi, Tatjana; König, Klemens; Sänger, Jörg; Feyen, Oliver; Hofmann, Heiko; Reinert, Siegmar; Coy, Johannes F. (2013-12-04). "A biomarker based detection and characterization of carcinomas exploiting two fundamental biophysical mechanisms in mammalian cells". BMC Cancer. 13: 569. doi: 10.1186/1471-2407-13-569 . ISSN 1471-2407. PMC 4235042 . PMID 24304513.
- 1 2 Coy, Johannes F. (2017-04-20). "EDIM-TKTL1/Apo10 Blood Test: An Innate Immune System Based Liquid Biopsy for the Early Detection, Characterization and Targeted Treatment of Cancer". International Journal of Molecular Sciences. 18 (4): 878. doi: 10.3390/ijms18040878 . ISSN 1422-0067. PMC 5412459 . PMID 28425973.
- ↑ "Macrophages | British Society for Immunology". www.immunology.org. Retrieved 2022-12-15.
- ↑ Saman, S.; Stagno, M. J.; Warmann, S. W.; Malek, N. P.; Plentz, R. R.; Schmid, E. (2020-01-01). "Biomarkers Apo10 and TKTL1: Epitope-detection in monocytes (EDIM) as a new diagnostic approach for cholangiocellular, pancreatic and colorectal carcinoma". Cancer Biomarkers. 27 (1): 129–137. doi:10.3233/CBM-190414. ISSN 1574-0153. PMC 7029314 . PMID 31771043.
- ↑ Urla, Cristian; Stagno, Matias Julian; Schmidt, Andreas; Handgretinger, Rupert; Fuchs, Jörg; Warmann, Steven W.; Schmid, Evi (2022-07-28). "Epitope Detection in Monocytes (EDIM) As a New Method of Liquid Biopsy in Pediatric Rhabdomyosarcoma". Biomedicines. 10 (8): 1812. doi: 10.3390/biomedicines10081812 . ISSN 2227-9059. PMC 9404738 . PMID 36009359.
- ↑ Jansen, Natalie; Coy, Johannes F (2013-04-01). "Diagnostic use of epitope detection in monocytes blood test for early detection of colon cancer metastasis". Future Oncology. 9 (4): 605–609. doi:10.2217/fon.13.8. ISSN 1479-6694. PMID 23560382.
- ↑ Simon Burg, Audrey Laure Céline Grust, Oliver Feyen, Katja Failing, Gamal-André Banat, Johannes F Coy, Martin Grimm, Martin Gosau, Ralf Smeets. "Blood-Test Based Targeted Visualization Enables Early Detection of Premalignant and Malignant Tumors in Asymptomatic Individuals" (PDF). Archived from the original (PDF) on 2023-03-26. Retrieved 2022-12-15.
{{cite web}}: CS1 maint: multiple names: authors list (link) - ↑ Burg, Simon; Smeets, Ralf; Gosau, Martin; Failing, Katja; Grust, Audrey Laure Céline (2023). "Case Report: Early detection of lung carcinoid in an asymptomatic individual by blood-test initiated PET-CT imaging". Frontiers in Oncology. 13. doi: 10.3389/fonc.2023.1177237 . ISSN 2234-943X. PMC 10280377 . PMID 37346076.
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