CD56 is a neural cell adhesion molecule (NCAM) involved in processes such as neuronal adhesion, neurite bundling, and neurite outgrowth. CD56 is a typical phenotypic marker of natural killer (NK) cells. Its expression level and function are closely related to NK cell activity, influencing their ability to recognize and kill target cells. CD56 expression is associated with the aggressiveness and prognosis of certain tumors, making it an important marker in tumor diagnosis and treatment research.
CD56 distribution
CD56 is an important cell surface marker, primarily expressed on natural killer (NK) cells, which are an important component of the immune system and are responsible for recognizing and killing virus-infected cells and tumor cells. In addition, CD56 is also expressed on cells such as neurons and glial cells.
(Data source:Uniprot)
CD56 structure
CD56 is a cell surface glycoprotein with multiple immunoglobulin superfamily domains and glycosylation sites that are involved in cell-cell interactions and signaling. It is anchored to the cell membrane via a transmembrane region and possesses an intracellular tail that participates in intracellular signaling.
(Data source: Uniprot)
Phenotypic markers of NK cells
CD56 is a phenotypic marker of NK cells. Based on the density of CD56 on the cell surface, NK cells are divided into CD56 Bright and CD56 Dim. CD56 Bright and CD56 Dim. NK cells represent immature and mature NK cells, respectively, with distinct phenotypic characteristics. CD56 Bright NK cells are more capable of producing abundant cytokines. CD56 Dim NK cells are more cytotoxic and express more immunoglobulin-like receptors and FcγRIII (Fcγ receptor III, also known as CD16), making them more susceptible to inducing cell-mediated cytotoxicity (ADCC).
(Data source van Eeden C, et al. Int J Mol Sci. 2020)
Relationship between CD56 and disease
CD56 and Multiple Myeloma
The role of CD56 in multiple myeloma is to promote cell growth, survival, and attachment to stromal cells through the RSK2/CREB1 signaling pathway, leading to increased expression of anti-apoptotic genes. CD56 expression helps distinguish abnormal multiple myeloma cells from normal plasma cells. Inhibition of RSK2 or CREB1 can induce cell death in CD56-expressing multiple myeloma cells. CD56 can be used as a predictive biomarker for multiple myeloma treatment and is of great significance for patient treatment and prognosis.
(Data source: Cottini F, et al. Mol Cancer Res. 2022)
CD56 and neurodegenerative diseases
CD56 plays a crucial role in neurodegenerative diseases such as multiple sclerosis, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. In multiple sclerosis (MS), in particular, CD56 Bright NK cells accumulate in the central nervous system of MS patients and may have immunomodulatory effects, helping to control inflammatory responses. CD56 Bright NK cells can play a role in MS patients by inducing cytotoxicity and killing activated autologous T cells.
(Data source: Rodriguez-Mogeda C, et al. J Neuroinflammation. 2024)
Daclizumab is the first MS therapy to show an effect on CD56 Bright NK cells. Later, more studies were conducted to investigate the effects of various therapies on CD56 Bright NK cells. Some of these therapies lead to CD56 Bright NK cell proliferation, which correlates with positive treatment outcomes, whereas other therapies alter the activation of these cells without causing overactivation. The CD56 Bright NK cell population has a beneficial immunomodulatory role in the pathogenesis of multiple sclerosis.
(Data source: Rodriguez-Mogeda C, et al. J Neuroinflammation. 2024)
Studies have shown that CD56 Bright NK and CD56 Dim NK cells play an important role in Parkinson's disease (PD). The frequencies of CD56 Bright NK and D56 Dim NK subsets in PD patients correlate with disease severity, indicating that CD56 plays a key role in PD development and severity. This suggests that CD56 has potential clinical significance in assessing the clinical status and duration of Parkinson's disease patients.
(Data source: Weber S, et al. NPJ Parkinsons Dis. 2024)
