title: Expression of PD-1 on CD4+ T cells in peripheral blood associates with poor clinical outcome in non-small cell lung cancer.
abstract: 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.
authors.affiliation: Penn State Hershey Cancer Institute, Penn State College of Medicine, Hershey, PA, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Penn State Hershey Cancer Institute, Penn State College of Medicine, Hershey, PA, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Penn State Hershey Cancer Institute, Penn State College of Medicine, Hershey, PA, USA.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Penn State Hershey Cancer Institute, Penn State College of Medicine, Hershey, PA, USA.
authors.forename: Shawn J
authors.initials: SJ
authors.lastname: Rice
authors.affiliation: Penn State Hershey Cancer Institute, Penn State College of Medicine, Hershey, PA, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Wagman
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.
authors.forename: Yaxian
authors.initials: Y
authors.lastname: Kong
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.
authors.forename: Liuluan
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Penn State Hershey Cancer Institute, Penn State College of Medicine, Hershey, PA, USA.
authors.forename: Junjia
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Penn State Hershey Cancer Institute, Penn State College of Medicine, Hershey, PA, USA.
authors.forename: Monika
authors.initials: M
authors.lastname: Joshi
authors.affiliation: Penn State Hershey Cancer Institute, Penn State College of Medicine, Hershey, PA, USA.
authors.forename: Chandra P
authors.initials: CP
authors.lastname: Belani
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000938:Antigen-Presenting Cells / Q000378:metabolism; D000074322:Antineoplastic Agents, Immunological / Q000627:therapeutic use; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000648:ultrastructure; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D002462:Cell Membrane / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000097:blood / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000074322:Antineoplastic Agents, Immunological; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: NSCLC; PD-1; T cells; peripheral blood; prognosis