PD-1

from Wikipedia, the free encyclopedia
Programmed cell death protein 1
other names

PD-1, CD279

Existing structure data : PDB  2M2D , PDB  3RRQ , PDB  4ZQK

Properties of human protein
Mass / length primary structure 288 amino acids , 31,647 Da
Identifier
External IDs
Orthologue (human)
Entrez 5133
Ensemble ENSG00000188389
UniProt Q15116
Refseq (mRNA) NM_005018.2
Refseq (protein) NP_005009.2
PubMed search 5133

Programmed cell death protein 1 or PD-1 molecule , or PD-1 for short , is a surface protein from the immunoglobulin superfamily and is involved in inhibiting the immune response .

properties

Extracellular part of PD-1

PD-1 is the receptor for PD-L1 with a dissociation constant of 8 µM as well as for PD-L2 . It's glycosylated .

Immune modulation

Binding of PD-L1 to PD-1 inhibits the immune response by inducing gene expression of interleukin-10 in monocytes. It also inhibits the phosphorylation of ZAP70 and promotes gene expression of the ubiquitin ligase CBL-b .

In persistent infections of LCMV and HIV , an increased gene expression of PD-1 is observed in CD8 -positive T cells (synonymous with cytotoxic T cells ). The increased activation of PD-1 by PD-L1 is believed to be involved in the anergy of cytotoxic T cells.

Applications

The concentration of PD-L1 is also examined before antibodies against PD-1 are used in the context of cancer immunotherapy , whereby not all anti-PD1-sensitive tumors form PD-L1 and in some cases still respond to cancer immunotherapy against PD-1. The therapeutic antibodies and immune checkpoint inhibitors nivolumab and pembrolizumab used for cancer immunotherapy bind to PD-1 and inhibit PD-1 activation by PD-L1. Antibodies directed against the PD-1 molecule are the standard of treatment for inoperable melanoma that is already forming daughter tumors. In melanomas with low or no PD-L1 expression, a combination of nivolumab and ipilimumab is more effective than anti-PD-1 monotherapy, but is more often associated with severe adverse immunological effects.

Inhibition of PD-1 is being studied for the treatment of chronic infectious diseases such as tuberculosis and HIV .

Web links

Individual evidence

  1. ↑ H. Dong, G. Zhu, K. Tamada, L. Chen: B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. In: Nature medicine. Volume 5, Number 12, December 1999, pp. 1365-1369, doi : 10.1038 / 70932 , PMID 10581077 .
  2. ↑ Yoshiyuki Yamaguchi: Immunotherapy of Cancer. Springer, 2016, ISBN 978-4-431-55031-0 , p. 286.
  3. ^ EA Said, FP Dupuy, L. Trautmann, Y. Zhang, Y. Shi, M. El-Far, BJ Hill, A. Noto, P. Ancuta, Y. Peretz, SG Fonseca, J. Van Grevenynghe, MR Boulassel , J. Bruneau, NH Shoukry, JP Routy, DC Douek, EK Haddad, RP Sekaly: Programmed death-1-induced interleukin-10 production by monocytes impairs CD4 + T cell activation during HIV infection. In: Nature medicine. Volume 16, number 4, April 2010, pp. 452-459, doi : 10.1038 / nm.2106 , PMID 20208540 , PMC 4229134 (free full text).
  4. ^ KA Sheppard, LJ Fitz, JM Lee, C. Benander, JA George, J. Wooters, Y. Qiu, JM Jussif, LL Carter, CR Wood, D. Chaudhary: PD-1 inhibits T-cell receptor induced phosphorylation of the ZAP70 / CD3zeta signalosome and downstream signaling to PKCtheta. In: FEBS letters. Volume 574, number 1-3, September 2004, pp. 37-41, doi : 10.1016 / j.febslet.2004.07.083 , PMID 15358536 .
  5. ↑ K. Karwacz, C. Bricogne, D. MacDonald, F. Arce, CL Bennett, M. Collins, D. Escors: PD-L1 co-stimulation contributes to ligand-induced T cell receptor down-modulation on CD8 + T cells. In: EMBO molecular medicine. Volume 3, number 10, October 2011, pp. 581-592, doi : 10.1002 / emmm.201100165 , PMID 21739608 , PMC 3191120 (free full text).
  6. ↑ a b Waun Ki Hong: Holland-Frei Cancer Medicine 8. PMPH-USA, 2010, ISBN 978-1-607-95014-1 , p. 185.
  7. ^ A. Ribas, S. Hu-Lieskovan: What does PD-L1 mean positive or negative? In: The Journal of experimental medicine. Volume 213, number 13, December 2016, pp. 2835–2840, doi : 10.1084 / jem.20161462 , PMID 27903604 , PMC 5154949 (free full text).
  8. ↑ Shuren Zhang: Progress in Cancer Immunotherapy. Springer, 2016, ISBN 978-9-401-77555-7 , p. 37.
  9. ↑ David Kerr: Immunotherapy for Gastrointestinal Cancer. Springer, 2017, ISBN 978-3-319-43063-8 , p. 129.
  10. ↑ MK Callahan, MA Postow, JD Wolchok: Targeting T Cell Co-receptors for Cancer Therapy. In: Immunity. Volume 44, number 5, May 2016, pp. 1069-1078, doi : 10.1016 / j.immuni.2016.04.023 , PMID 27192570 .
  11. ↑ Patrick Terheyden, Angela Krackhardt, Thomas Eigenler: System therapy of melanoma. Use of immune checkpoint inhibitors and inhibition of intracellular signal transduction. In: Deutsches Ärzteblatt. Volume 116, Issue 29 f., (July 22) 2019, pp. 497-504, especially p. 503.
  12. ^ M. Rao, D. Valentini, E. Dodoo, A. Zumla, M. Maeurer: Anti-PD-1 / PD-L1 therapy for infectious diseases: learning from the cancer paradigm. In: International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases. Volume 56, March 2017, pp. 221-228, doi : 10.1016 / j.ijid.2017.01.028 , PMID 28163164 .
  13. ↑ V. Velu, RD Shetty, M. Larsson, EM Shankar: Role of PD-1 co-inhibitory pathway in HIV infection and potential therapeutic options. In: Retrovirology. Volume 12, February 2015, p. 14, doi : 10.1186 / s12977-015-0144-x , PMID 25756928 , PMC 4340294 (free full text).