Expression of PD-1 on CD4+ T cells in peripheral blood associates with poor clinical outcome in non-small cell lung cancer
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Hong Zheng1,*, Xin Liu1,*, Jianhong Zhang1, Shawn J. Rice1, Matthias Wagman1, Yaxian Kong2, Liuluan Zhu2, Junjia Zhu1, Monika Joshi1, Chandra P. Belani1
1Penn State Hershey Cancer Institute, Penn State College of Medicine, Hershey, PA, USA
2Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China
*These authors have contributed equally to this work
Chandra Belani, e-mail: [email protected]
Keywords: PD-1, peripheral blood, T cells, prognosis, NSCLC
Received: February 12, 2016 Accepted: April 13, 2016 Published: May 12, 2016
Recent success of using agents inhibiting the major immune check point, programmed cell death-1 (PD-1) pathway, offers a great promise for effective cancer therapy. Two blocking antibodies for PD-1, nivolumab and pembrolizumab have recently been approved for treating advanced recurrent non-small cell lung cancer (NSCLC). Activation of PD-1 on T cells and PD-L1 on tumor cells or antigen presenting cells leads to T cell exhaustion and ultimately tumor growth. In this study, we performed flow cytometry analysis of peripheral blood samples collected from patients with advanced NSCLC at initial diagnosis. We report that surface expression of PD-1 on CD4+ T cells has a prognostic value in NSCLC patients, as high expression of PD-1 is associated with a shorter progression-free survival and overall survival. Importantly, we also found that high PD-1 expression on peripheral CD4+ T cells is associated with inferior clinical response in a subset of patients who received anti-PD-L1 treatment, indicating a potential predictive value of this marker. This work highlights the potential of a non-invasive and effective method to determine prognostic and predictive biomarkers for inhibiting the PD-1 pathway in NSCLC patients.
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