CD27

Official Full Name

CD27 molecule

Organism

Homo sapiens

GeneID

939

Background

The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is required for generation and long-term maintenance of T cell immunity. It binds to ligand CD70, and plays a key role in regulating B-cell activation and immunoglobulin synthesis. This receptor transduces signals that lead to the activation of NF-kappaB and MAPK8/JNK. Adaptor proteins TRAF2 and TRAF5 have been shown to mediate the signaling process of this receptor. CD27-binding protein (SIVA), a proapoptotic protein, can bind to this receptor and is thought to play an important role in the apoptosis induced by this receptor. [provided by RefSeq, Jul 2008]

Synonyms

T14; S152; Tp55; TNFRSF7; S152. LPFS2;

Bio Chemical Class

Cytokine receptor

Protein Sequence

MARPHPWWLCVLGTLVGLSATPAPKSCPERHYWAQGKLCCQMCEPGTFLVKDCDQHRKAAQCDPCIPGVSFSPDHHTRPHCESCRHCNSGLLVRNCTITANAECACRNGWQCRDKECTECDPLPNPSLTARSSQALSPHPQPTHLPYVSEMLEARTAGHMQTLADFRQLPARTLSTHWPPQRSLCSSDFIRILVIFSGMFLVFTLAGALFLHQRRKYRSNKGESPVEPAEPCHYSCPREEEGSTIPIQEDYRKPEPACSP

Open

Disease

Brain cancer, Colorectal cancer, Head and neck cancer, Leukaemia, Lymphoma, Ovarian cancer, Renal cell carcinoma, Solid tumour/cancer

Approved Drug

Clinical Trial Drug

3 +

Discontinued Drug

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Detailed Information

The CD27 gene codes for a protein of the tumor necrosis factor (TNF) receptor superfamily. Acting as a necessary mediator in the immune response, this receptor is fundamental for the establishment and long-term maintenance of T cell immunity. CD70 binds to its ligand and then becomes very important in controlling B-cell activation and immunoglobulin production. Traf2 and TRAF5 help to stimulate important intracellular pathways like NF-kappaB and MAPK8/JNK, therefore activating the signaling pathway driven by CD27. Fascinatingly, CD27 may also interact with the pro-apoptotic protein CD27-binding protein (SIVA), indicating its participation in the control of death connected to immune responses.

Mostly on the surface of T cells, B cells, and natural killer (NK) cells, CD27 is expressed. Mostly present on activated T cells, B cells, and mature dendritic cells is the ligand CD70. CD27's interaction with CD70 sets off a series of intracellular signals that activate cells, proliferate them, provide effector action, and enable survival. Apart from encouraging T cell and B cell activation, this connection is essential for their proliferation and differentiation, hence generating a strong immunological response.

Figure 1 describes the CD27–CD70 pathway in immune regulation. Figure 1. CD27–CD70 Pathway in Immune Regulation. (Han BK et al., 2016)

CD27's Role in Anti-Tumor Activity

In the framework of carcinogenesis, NK cells show a two-fold method of action: they may either directly detect and activate against malignant cells or be activated indirectly via contact with auxiliary cells like dendritic cells, monocytes, and macrophages. These interactions improve their ability to target tumors. To bind with CD70 on tumor cells and therefore release perforin and cytokines, NK cells specifically use transmembrane glycoproteins including CD27. This acts finally to activate cytotoxic T lymphocytes (CTLs), therefore helping to destroy tumor cells.

Expressed on most T cells—including naïve CD4 T cells, effector CD4 T cells, and CD8 T cells—as a member of the TNFR superfamily, CD27 The signaling pathway of CD27 depends on the presence of its ligand, CD70, with a strong secondary signal required for the activation of CD4-dependent T cells and CD8-independent T cells during tumor clearance provided by their interaction.

Recent developments in cancer immunotherapy have shown how important immunological checkpoints such as PD-1 are in T cell activation. For certain individuals, nevertheless, inadequate activation of T cells resulting from the lack of activated dendritic cells might restrict the efficacy of PD-1 blocking treatments. Promisingly, the use of CD27 agonists has become a possible approach to overcome this restriction. Combining PD-1 inhibition with CD27 agonists greatly increases CD8 + T cell-driven anti-tumor immune responses, according to studies by Sarah L. Buchan and colleagues.

Recently Laura A. found that CDX-527 generates a bispecific antibody by efficiently combining a PD-1 blocking drug with CD27 co-stimulation. This bispecific method shows the synergistic possibilities of combining two pathways as it provides a theoretical foundation for improving tumor-targeted T-cell immunity.

Monoclonal Antibodies and the Recruitment of Effector Cells

By attracting effector cells and increasing cytotoxic T-cell activity, monoclonal antibodies provide even another means of boosting immune responses against tumors. To cure cancer, researchers have investigated the possibilities of tumor-targeting antibodies including CD20 antibodies in concert with other immune-modulating monoclonal antibodies. Results show that in mice against lymphomas and B16 melanoma, CD27-activating antibodies may boost anti-tumor immune responses. These results unequivocally show that by attracting myeloid cells, hence strengthening the anti-tumor immune response, CD27 agonists may improve the effectiveness of tumor-targeting antibodies.

References:

Ahrends T, Bąbała N, Xiao Y, et al. CD27 Agonism Plus PD-1 Blockade Recapitulates CD4+ T-cell Help in Therapeutic Anticancer Vaccination. Cancer Res. 2016;76(10):2921-2931.
Welten SP, Redeker A, Franken KL, et al. CD27-CD70 costimulation controls T cell immunity during acute and persistent cytomegalovirus infection. J Virol. 2013;87(12):6851-6865.
Buchan SL, Fallatah M, Thirdborough SM, et al. PD-1 Blockade and CD27 Stimulation Activate Distinct Transcriptional Programs That Synergize for CD8⁺ T-Cell-Driven Antitumor Immunity. Clin Cancer Res. 2018;24(10):2383-2394.
Vitale LA, He LZ, Thomas LJ, et al. Development of CDX-527: a bispecific antibody combining PD-1 blockade and CD27 costimulation for cancer immunotherapy. Cancer Immunol Immunother. 2020;69(10):2125-2137.
Han BK, Olsen NJ, Bottaro A. The CD27-CD70 pathway and pathogenesis of autoimmune disease. Semin Arthritis Rheum. 2016;45(4):496-501.

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