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 Apr;9(4):E384-E386.
doi: 10.21037/jtd.2017.03.118.

PD-1 targeted Immunotherapy as first-line therapy for advanced non-small-cell lung cancer patients

Arik Bernard Schulze  1 , Lars Henning Schmidt  1
Affiliations
Editorial

PD-1 targeted Immunotherapy as first-line therapy for advanced non-small-cell lung cancer patients

Arik Bernard Schulze et al. J Thorac Dis. 2017 Apr.
No abstract available

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
PD-1:PD-L1 mechanisms between T-cells and tumor cells. (A) Loss of phosphatase and tensin homolog (PTEN) in tumor cells induces the Phosphoinositol-3-kinase (PI3K)—Akt pathway with consecutive overexpression of PD-L1 (1); (B) once PD-L1 binds to PD-1, the resulting inhibition influences tumor surveillance such as Fas-mediated apoptosis (2). By co-activation of PD-1 concomitant to TCR in T-cells, the phosphorylation of the SHP-2 domain results in a down-regulation of the PI3K-Akt pathway. This step alters the mTOR complex, which regulates T cellular differentiation (3); (C) upon immune checkpoint inhibition, either with PD-L1-mAb (Atezolizumab) or PD-1-mAbs (Pembrolizumab and Nivolumab), T-cell differentiation is switched to CD8+ T effector (T eff) or T memory (T mem) cells, inducing apoptosis by completing the major histocompatibility complex (MHC) of the tumor cells (3).
See this image and copyright information in PMC

Comment on

  • Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer.
    Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR; KEYNOTE-024 Investigators. Reck M, et al. N Engl J Med. 2016 Nov 10;375(19):1823-1833. doi: 10.1056/NEJMoa1606774. Epub 2016 Oct 8. N Engl J Med. 2016. PMID: 27718847 Clinical Trial.

References

    1. Parsa AT, Waldron JS, Panner A, et al. Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma. Nat Med 2007;13:84-8. 10.1038/nm1517 - DOI - PubMed
    1. Azuma T, Yao S, Zhu G, et al. B7-H1 is a ubiquitous antiapoptotic receptor on cancer cells. Blood 2008;111:3635-43. 10.1182/blood-2007-11-123141 - DOI - PMC - PubMed
    1. Bardhan K, Anagnostou T, Boussiotis VA. The PD1:PD-L1/2 Pathway from Discovery to Clinical Implementation. Front Immunol 2016;7:550. 10.3389/fimmu.2016.00550 - DOI - PMC - PubMed
    1. Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by CTLA-4 blockade. Science 1996;271:1734-6. 10.1126/science.271.5256.1734 - DOI - PubMed
    1. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med 2015;373:123-35. 10.1056/NEJMoa1504627 - DOI - PMC - PubMed

LinkOut - more resources