CD24 is a protein found on the surface of various cells throughout the body. It is classified as a sialoglycoprotein, a protein with sialic acid-containing sugar chains attached. It is anchored to the cell membrane via a glycosylphosphatidylinositol (GPI) link. Its presence allows it to interact with other molecules and participate in cellular communication.
What CD24 Does in the Body
In healthy individuals, CD24 plays a role in several basic cellular functions. It is involved in cell adhesion, cell migration, and cell differentiation. CD24 also influences apoptosis, a programmed process of cell death.
CD24 contributes to the regulation of the immune system. It is expressed on various immune cells, including mature granulocytes and B cells, modulating signals that influence their growth and differentiation. CD24 can interact with other receptors, such as P-selectin and Siglecs, to mediate cell-to-cell communication and maintain tissue balance.
CD24’s Involvement in Cancer
CD24’s expression and function often become altered in various cancers, contributing to disease progression. High levels of CD24 are frequently found on the surface of many tumor cells and are often associated with a poorer outlook for patients. This overexpression can facilitate malignant activities, including increased cell proliferation, invasion, and metastasis. For instance, CD24 can bind to P-selectin on platelets, which helps tumor cells exit the bloodstream and metastasize.
CD24 also plays a role in making cancer cells resistant to chemotherapy treatments. In triple-negative breast cancer (TNBC), for example, high CD24 expression is linked to worse overall survival and shorter metastasis-free survival after taxane-based therapies. Certain breast cancer cells with a specific CD44+/CD24+/high phenotype show increased resistance to docetaxel, while CD44+/CD24-/low cells are more resistant to doxorubicin. In ovarian cancer, CD24 overexpression is associated with increased metastatic potential and poor prognosis. CD24-positive ovarian cancer cells also show higher tumor-initiating capabilities and are sensitive to certain signaling pathway inhibitors, such as JAK2 inhibitors, which can prevent metastasis.
CD24 can help cancer cells evade the immune system. It acts as a “don’t eat me” signal by binding to Siglec-10, a receptor found on immune cells like macrophages. This interaction inhibits the macrophage’s ability to engulf and clear tumor cells, allowing cancer to escape immune detection. CD24 also activates certain signaling pathways, such as Src Family Kinases, which promote cell proliferation, survival, and migration in cancer cells.
CD24’s Role Beyond Cancer
CD24 is implicated in other pathological conditions, particularly autoimmune diseases. It is involved in inflammation and both adaptive and autoimmune immunity. Genetic variations (polymorphisms) in the CD24 gene have been linked to an increased risk and progression of autoimmune conditions such as multiple sclerosis (MS) and systemic lupus erythematosus (SLE).
In multiple sclerosis, CD24 is expressed on various immune cells and central nervous system cells that play a role in disease development. Studies in mice have shown that CD24 expression on both T cells and other host cells is necessary for the development of experimental autoimmune encephalomyelitis (EAE), an MS model. CD24 expression on non-T cells helps control the expansion of disease-causing T cells, while T-cell expression of CD24 is needed for T cell proliferation when immune cells are scarce.
For systemic lupus erythematosus, a meta-analysis revealed a significant association between a specific CD24 gene variant (the Val allele) and increased susceptibility to the disease. These findings suggest CD24 contributes to immune dysregulation in these conditions, potentially by influencing immune cell activation and function. CD24’s role as a costimulatory molecule, which activates T cells, may also contribute to its involvement in autoimmune responses.
CD24 as a Diagnostic Tool and Therapeutic Target
CD24 holds promise as both a diagnostic marker and a target for therapeutic interventions across various diseases. Its presence and levels on cell surfaces can indicate the presence or progression of certain conditions. For example, high CD24 expression in ovarian cancer cells is associated with significantly poorer progression-free and overall survival after standard therapies, making it a potential prognostic marker. Researchers are developing diagnostic antibodies to enhance the screening and selection of patients based on CD24 expression, which could lead to more tailored treatment approaches.
As a therapeutic target, CD24 is being explored in several innovative ways, particularly in cancer treatment. Strategies aim to block CD24’s functions, especially its “don’t eat me” signal that allows cancer cells to evade immune attack. Antibody-based therapies are being developed to target CD24 directly, with some clinical trials already evaluating their safety and effectiveness. These antibodies can block the interaction between CD24 on tumor cells and Siglec-10 on immune cells, potentially allowing macrophages to recognize and eliminate cancer cells.
Another promising approach involves Chimeric Antigen Receptor (CAR) T cell therapy. In this method, a patient’s T cells are genetically modified to recognize and attack cancer cells expressing CD24. CD24-targeted CAR-T cells have shown strong ability to kill CD24-positive cancer cells in laboratory settings and inhibit tumor growth in preclinical models. This therapy can also activate the body’s anti-tumor immune responses, leading to long-term tumor regression. CD24-targeting CAR-T cells are being investigated for triple-negative breast cancer, a particularly aggressive subtype, showing potent anti-tumor activity in models.