Biology:CD27

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Short description: Member of the tumor necrosis factor receptor superfamily.


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

CD27 is a member of the tumor necrosis factor receptor superfamily.[1] It is currently of interest to immunologists as a co-stimulatory immune checkpoint molecule, and is the target of an anti-cancer drug in clinical trials.[2]

Expression

During mouse embryonic development, specific (medium) expression levels of CD27 (in addition to high cKit,[3][4] medium Gata2,[5][6][4] and high CD31[4] expression levels) define the very first adult definitive hematopoietic stem cells generated in the aorta-gonad-mesonephros region.[4] Furthermore, CD27 is expressed on both naïve and activated effector T cells as well as NK cells and activated B cells.[1] It is a type I transmembrane protein with cysteine-rich domains, but once T cells have become activated, a soluble form of CD27 can be shed.[1][2]

Function

The protein encoded by this gene is a member of the TNF-receptor superfamily.[7] 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.[1]

When CD27 binds CD70, a signaling cascade leads to the differentiation and clonal expansion of T cells.[7] The cascade also results in improved survival and memory of cytotoxic T cells and increased production of certain cytokines.[8] This receptor transduces signals that lead to the activation of NF-κB and MAPK8/JNK.[7] Adaptor proteins TRAF2, TRAF3, and TRAF5 have been shown to mediate the signaling process of this receptor via ubiquitination.[1][2] 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.[9]

In murine γδ T cells its expression has been correlated with the secretion of IFNγ.[10]

Clinical significance

As a drug target

Varlilumab is an IgG1 antibody that binds to CD27 and is an experimental cancer treatment.[2] This agonist antibody stimulates CD27 when it binds.[2] The drug is in early clinical trials and appears to stimulate T cells and increase production of cytokines such as interferon-gamma.[2][7]

Interactions

CD27 has been shown to interact with SIVA1,[11] TRAF2[12][13] and TRAF3.[12][13]

Mutations

Some mutations can decrease the expression of CD27. Three such mutations, C53Y, C96Y, and R107C, are located in the cysteine-rich domains of CD27.[1]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 "The immunobiology of CD27 and OX40 and their potential as targets for cancer immunotherapy". Blood 131 (1): 39–48. January 2018. doi:10.1182/blood-2017-07-741025. PMID 29118006. 
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 "TNFR agonists: a review of current biologics targeting OX40, 4-1BB, CD27, and GITR". American Journal of Hematology/Oncology 13 (11): 4–15. November 2017. https://www.gotoper.com/publications/ajho/2017/2017november/tnfr-agonists-a-review-of-current-biologics-targeting-ox40-4-1bb-cd27-and-gitr. 
  3. ↑ "Characterization of the first definitive hematopoietic stem cells in the AGM and liver of the mouse embryo". Immunity 5 (6): 513–25. December 1996. doi:10.1016/s1074-7613(00)80267-8. PMID 8986712. 
  4. ↑ 4.0 4.1 4.2 4.3 "Iterative Single-Cell Analyses Define the Transcriptome of the First Functional Hematopoietic Stem Cells". Cell Reports 31 (6): 107627. May 2020. doi:10.1016/j.celrep.2020.107627. PMID 32402290. 
  5. ↑ "Functional and molecular characterization of mouse Gata2-independent hematopoietic progenitors". Blood 127 (11): 1426–37. March 2016. doi:10.1182/blood-2015-10-673749. PMID 26834239. 
  6. ↑ "In vivo single cell analysis reveals Gata2 dynamics in cells transitioning to hematopoietic fate". The Journal of Experimental Medicine 215 (1): 233–248. January 2018. doi:10.1084/jem.20170807. PMID 29217535. 
  7. ↑ 7.0 7.1 7.2 7.3 "Emerging targets in cancer immunotherapy". Seminars in Cancer Biology. Immuno-oncological biomarkers 52 (Pt 2): 39–52. October 2018. doi:10.1016/j.semcancer.2017.10.001. PMID 28987965. 
  8. ↑ "Stimulating CD27 to quantitatively and qualitatively shape adaptive immunity to cancer". Current Opinion in Immunology 45: 82–88. April 2017. doi:10.1016/j.coi.2017.02.001. PMID 28319731. 
  9. ↑ "Entrez Gene: CD27 CD27 molecule". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=939. 
  10. ↑ "CD27 is a thymic determinant of the balance between interferon-gamma- and interleukin 17-producing gammadelta T cell subsets". Nature Immunology 10 (4): 427–36. April 2009. doi:10.1038/ni.1717. PMID 19270712. 
  11. ↑ "CD27, a member of the tumor necrosis factor receptor family, induces apoptosis and binds to Siva, a proapoptotic protein". Proceedings of the National Academy of Sciences of the United States of America 94 (12): 6346–51. June 1997. doi:10.1073/pnas.94.12.6346. PMID 9177220. Bibcode: 1997PNAS...94.6346P. 
  12. ↑ 12.0 12.1 "NF-kappaB activation in CD27 signaling: involvement of TNF receptor-associated factors in its signaling and identification of functional region of CD27". Journal of Immunology 161 (9): 4753–9. November 1998. PMID 9794406. 
  13. ↑ 13.0 13.1 "CD27, a member of the tumor necrosis factor receptor superfamily, activates NF-kappaB and stress-activated protein kinase/c-Jun N-terminal kinase via TRAF2, TRAF5, and NF-kappaB-inducing kinase". The Journal of Biological Chemistry 273 (21): 13353–8. May 1998. doi:10.1074/jbc.273.21.13353. PMID 9582383. 

Further reading

External links




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