CD155 is a protein found on the surface of various cells throughout the body. It is involved in many biological processes, including cell interaction and their surroundings. Initially discovered for its role in viral infections, CD155’s diverse functions are significant in both normal bodily functions and disease.
Understanding CD155
CD155 is a type I transmembrane glycoprotein. It belongs to the immunoglobulin superfamily, a group of proteins involved in cell recognition, adhesion, and immune responses. Structurally, it has three immunoglobulin-like extracellular domains (D1, D2, D3), a transmembrane domain, and a cytoplasmic tail.
CD155 is also known as the Poliovirus Receptor (PVR). It was discovered as the specific molecule the poliovirus uses to enter human cells and initiate infection. The D1 domain, the outermost extracellular domain, is responsible for recognizing and binding to the poliovirus. This interaction allows the virus to attach to the cell surface before releasing its genetic material into the cell.
CD155’s Normal Functions
In healthy cells and tissues, CD155 plays a role in cell adhesion, helping cells stick together to form tissues and organs. It establishes adherens junctions between epithelial cells, contributing to tissue integrity. The protein also participates in cell migration, important for development and wound healing.
CD155 interacts with various receptors on immune cells, influencing the body’s immune responses. For example, it binds to activating receptors like DNAM-1 (CD226) on natural killer (NK) cells and T cells, aiding in the recognition and removal of abnormal cells. Conversely, CD155 also interacts with inhibitory receptors, such as TIGIT and CD96, which can dampen immune responses to maintain balance and prevent excessive inflammation.
CD155’s Role in Disease
CD155’s link to disease began with its role as the poliovirus receptor, enabling viral infection. Beyond viral infections, CD155 is relevant in cancer due to its involvement in tumor progression. While normally expressed at low levels in healthy tissues, CD155 is often overexpressed on many tumor cells, including those in melanoma, lung, and colorectal cancer. This overexpression promotes tumor growth by influencing cell proliferation and increasing cell migration, contributing to cancer invasiveness.
CD155 also aids in metastasis. Its role in cancer includes helping tumor cells evade the immune system. In the tumor microenvironment, CD155 on cancer cells interacts with immune checkpoint receptors like TIGIT and CD96 on immune cells such as T cells and NK cells. This interaction sends inhibitory signals, suppressing the immune cells’ ability to recognize and destroy cancer cells. The balance between CD155’s interactions with activating receptors like DNAM-1 and inhibitory receptors like TIGIT can be disrupted in cancer, leading to an immunosuppressive environment that favors tumor survival and progression.
Therapeutic Potential of CD155
Understanding CD155’s roles in tumor growth and immune evasion has opened avenues for new cancer therapeutic strategies. Researchers are exploring ways to target CD155 or its interacting partners to develop cancer treatments, particularly in immunotherapy. One approach involves blocking the interaction between CD155 on tumor cells and inhibitory receptors like TIGIT on immune cells.
Monoclonal antibodies are being developed to disrupt the CD155-TIGIT pathway, aiming to enhance anti-tumor immune responses. By blocking this inhibitory interaction, the goal is to “release the brakes” on immune cells, allowing them to attack and eliminate cancer cells. CD155 is also being investigated as a potential biomarker, where its expression levels could help predict patient response to certain immunotherapies or indicate disease prognosis.