CD155: Breaking Immune Suppression in Tumor Environments

CD155, also known as Poliovirus Receptor (PVR), is a transmembrane protein that plays a pivotal role in tumor immune evasion. While CD155 is normally involved in cell adhesion and migration, its overexpression on tumor cells creates an immunosuppressive environment by engaging inhibitory receptors on natural killer (NK) cells and T cells. Through these interactions, CD155 contributes to the suppression of the body's natural immune responses, helping tumors evade detection and destruction.

Targeting CD155 has emerged as a promising strategy to break immune suppression in the tumor microenvironment, allowing immune cells to regain their tumor-killing functions. Monoclonal antibodies such as SKII.4 have been developed to block CD155 interactions with inhibitory receptors like TIGIT and CD96, aiming to restore immune activity and enhance anti-tumor responses.

This article explores the biology of CD155, its role in cancer progression, and the potential of CD155-targeting therapies to revolutionize cancer treatment by reinvigorating immune responses in patients with advanced malignancies.

CD155 is a member of the Nectin-like family of adhesion molecules and is found on both normal and cancerous cells. Under physiological conditions, CD155 is involved in processes like cell adhesion and tissue regeneration. However, in cancer, CD155 is frequently overexpressed on the surface of tumor cells, especially in aggressive cancers such as:

• Melanoma
• Lung cancer
• Colorectal cancer
• Ovarian cancer

CD155 binds to both activating and inhibitory receptors on immune cells, depending on the context. The critical inhibitory receptor involved in tumor immune evasion is TIGIT (T cell immunoreceptor with Ig and ITIM domains), while activating receptors include DNAM-1 (CD226). When CD155 binds to TIGIT, the immune response is suppressed, effectively inhibiting NK cell and T cell function, and allowing tumor cells to evade immune destruction.