CD27

CD27 Full Name

CD27 molecule

CD27 Introduction

CD27 (Cluster of Differentiation 27), also classified as TNFRSF7, is a constitutive type I transmembrane glycoprotein belonging to the tumor necrosis factor receptor (TNFR) superfamily. It is predominantly expressed on the surface of naïve and memory T cells, natural killer (NK) cells, and memory B cells. Unlike many other costimulatory receptors that are induced only upon activation, CD27 is unique because it is constitutively expressed on naïve T cells, ready to receive immediate signals. Its specific ligand, CD70 (TNFSF7), is strictly regulated and transiently expressed on activated antigen-presenting cells (APCs), such as dendritic cells, B cells, and macrophages. The interaction between CD27 and CD70 serves as a pivotal costimulatory checkpoint that dictates the magnitude and quality of the adaptive immune response.

Figure 1. CD70-CD27 pathway. (Source: Jacobs J, et al. 2015)

Functionally, the ligation of CD27 by CD70 triggers the recruitment of TNF receptor-associated factor (TRAF) adaptor proteins (specifically TRAF2 and TRAF5) to the cytoplasmic tail of CD27. This assembly activates the canonical and non-canonical NF-κB and JNK signaling pathways, which are essential for promoting T cell survival, driving cellular proliferation, and supporting the differentiation of effector T cells into long-lived memory T cells. In the B cell lineage, CD27 is a classic marker of memory B cells and is critical for the generation of plasma cells and high-affinity antibody production. Following activation, the extracellular domain of CD27 is proteolytically shed from the cell surface by matrix metalloproteinases, releasing a soluble form (sCD27) into the circulation, which acts as a regulatory feedback mechanism and a marker of immune activation.

Pathologically, the dysregulation of the CD27-CD70 axis contributes to various disease states. A genetic deficiency in CD27 results in a specific primary immunodeficiency characterized by persistent symptomatic Epstein-Barr virus (EBV) viremia, hypogammaglobulinemia, and a high risk of developing EBV-driven lymphoproliferative disorders or lymphomas, highlighting its non-redundant role in antiviral immunity. Conversely, aberrant overexpression of CD27 is frequently observed in various hematological malignancies, including Hodgkin lymphoma, T-cell lymphomas, and chronic lymphocytic leukemia (CLL). In the era of cancer immunotherapy, CD27 is emerging as a compelling therapeutic target. Unlike checkpoint inhibitors (like anti-PD-1) that release the "brakes" on the immune system, agonistic antibodies targeting CD27 aim to step on the "gas pedal," artificially stimulating the receptor to boost tumor-specific T cell expansion and effector function, often showing synergistic potential when combined with other immunomodulators.

Alternate Names for CD27

CD27; CD27 molecule; T14; S152; Tp55; TNFRSF7; S152. LPFS2; CD27 antigen; CD27L receptor; T cell activation antigen S152; T-cell activation antigen CD27; tumor necrosis factor receptor superfamily, member 7;

• 1. Jacobs J, et al. CD70: An emerging target in cancer immunotherapy. Pharmacol Ther. 2015 Nov;155:1-10.
  2. Buchan SL, et al. The immunobiology of CD27 and OX40 and their potential as targets for cancer immunotherapy. Blood. 2018 Jan 4;131(1):39-48.