Expression of PD-1 on CD4+ T cells in peripheral blood associates with poor clinical outcome in non-small cell lung cancer

Oncotarget. 2016 Aug 30;7(35):56233-56240. doi: 10.18632/oncotarget.9316.

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.

Keywords: NSCLC; PD-1; T cells; peripheral blood; prognosis.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antigen-Presenting Cells / metabolism
  • Antineoplastic Agents, Immunological / therapeutic use
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / metabolism*
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / metabolism
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / ultrastructure
  • Carcinoma, Non-Small-Cell Lung / blood
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Membrane / metabolism
  • Disease-Free Survival
  • Female
  • Flow Cytometry
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / blood
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Programmed Cell Death 1 Receptor / blood
  • Programmed Cell Death 1 Receptor / metabolism*
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor