UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology

Publication Date

2018-06-08

Document Type

Article

Disciplines

Cancer Biology | Immunoprophylaxis and Therapy | Neoplasms | Therapeutics

Abstract

Cancer immunotherapy has been revolutionised by drugs that enhance the ability of the immune system to detect and fight tumors. Immune checkpoint therapies that target the programmed death-1 receptor (PD-1), or its ligand (PD-L1) have shown unprecedented rates of durable clinical responses in patients with various cancer types. However, there is still a large fraction of patients that do not respond to checkpoint inhibitors, and the challenge remains to find cellular and molecular cues that could predict which patients would benefit from these therapies. Using a series of qualitative and quantitative methods we show here that PBMCs and platelets from smokers and patients with head and neck squamous cell carcinoma (HNSCC) or lung cancer express and up-regulate PD-L1 independently of tumor stage. Furthermore, treatment with Atezolizumab, a fully humanised monoclonal antibody against PD-L1, in 4 patients with lung cancer caused a decrease in PD-L1 expression in platelets, which was restored over 20 days. Altogether, our findings reveal the expression of the main therapeutic target in current checkpoint therapies in human platelets and highlight their potential as biomarkers to predict successful therapeutic outcomes.

Keywords

atezolizumab, biomarkers for PD1-PD-L1 checkpoint therapy, head and neck cancer, tumor-educated platelets

Rights and Permissions

Copyright : © 2018 Rolfes et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

DOI of Published Version

10.18632/oncotarget.25446

Source

Oncotarget. 2018 Jun 8;9(44):27460-27470. doi: 10.18632/oncotarget.25446. eCollection 2018 Jun 8. Link to article on publisher's site

Journal/Book/Conference Title

Oncotarget

Related Resources

Link to Article in PubMed

PubMed ID

29937998

Creative Commons License

Creative Commons Attribution 3.0 License
This work is licensed under a Creative Commons Attribution 3.0 License.

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