Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Editorial
. 2017 May 5;6(5):e138.
doi: 10.1038/cti.2017.15. eCollection 2017 May.

PD1 functions by inhibiting CD28-mediated co-stimulation

Jake S O'Donnell  1   2   3 , Mark J Smyth  1   3 , Michele W L Teng  2   3
Affiliations
Editorial

PD1 functions by inhibiting CD28-mediated co-stimulation

Jake S O'Donnell et al. Clin Transl Immunology. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

MJS is funded by research agreements from Bristol Myers Squibb, Corvus Pharmaceuticals and Aduro Biotech. The remaining authors declare no conflict of interests.

Figures

Figure 1
Figure 1
PD1 limits T-cell activity by inhibiting CD28 co-stimulation. (a) PDL1+ tumour-associated APCs interact with tumour-specific PD1+ CD8 T cells. These exhausted cells also express CD28 capable of engaging with B7 molecules (CD80 or CD86) expressed by the tumour-associated APC; however, PD1 via its associated phosphatases, prevents CD28-mediated co-stimulation. (b) In the presence of αPDL1 (or αPD1) antibodies, PD1 and PDL1 cannot interact, allowing for exhausted CD8 T cells to receive CD28-mediated co-stimulation, promoting the induction of a proliferative burst of CD8 T cells capable of promoting tumour control.
See this image and copyright information in PMC

References

    1. Wherry EJ, Kurachi M. Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol 2015; 15: 486–489. - PMC - PubMed
    1. Pauken KE, Sammons MA, Odorizzi PM, Manne S, Godec J, Khan O et al. Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade. Science 2016; 354: 1160–1165. - PMC - PubMed
    1. Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature 2017; 541: 321–330. - PubMed
    1. Zaretsky JM, Garcia-Diaz A, Shin DS, Escuin-Ordinas H, Hugo W, Hu-Lieskovan S et al. Mutations associated with acquired resistance to PD-1 blockade in melanoma. N Engl J Med 2016; 375: 819–829. - PMC - PubMed
    1. Ribas A, Hamid O, Daud A, Hodi FS, Wolchok JD, Kefford R et al. Association of pembrolizumab with tumor response and survival among patients with advanced melanoma. JAMA 2016; 315: 1600–1609. - PubMed

Publication types