Analyzing the percentage of different PD-1+ T cell subsets in peripheral blood and bronchoalveolar lavage fluid of small cell lung cancer patients: A prospective study

Clin Exp Pharmacol Physiol. 2019 Dec;46(12):1074-1083. doi: 10.1111/1440-1681.13153. Epub 2019 Aug 30.

Abstract

The present study was designed to evaluate the percentage of different programmed cell death-1 (PD-1)+ T cell subsets in peripheral blood and bronchoalveolar lavage fluid (BALF) of small cell lung cancer (SCLC) patients. The percentages of PD-1+ T cell subsets in peripheral blood and BALF samples obtained from 52 lung cancer and 20 pneumonia patients, and 20 healthy controls were examined by flow cytometry. In addition, clinical parameters, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, were also determined using Spearman's correlation test to assess their association with PD-1+ T cell subsets. These present results revealed that the percentage of circulating PD-1+ Tfh and peripheral helper T cells (Tph) cells significantly increased in peripheral blood of SCLC patients, when compared to non-small cell lung cancer (NSCLC) pneumonia patients and healthy controls. In addition, PD-1+ Tfh cells were also significantly enhanced in patients in the extensive-stage group. In contrast, the BALF samples of SCLC patients exhibited a significant decrease in percentage of Tph cells. An overall imbalance was observed between PD-1+ Tfh and Tph cells in both compartments. Furthermore, SCLC patients exhibited a significant decrease in the percentage of circulating PD-1+ Tfh and Tph cells following chemotherapy, and the in vitro analysis revealed that the concentration of IL-2 and IFN-γ derived from PD-1 + Tfh cells in SCLC were significantly lower than that from NSCLC. However, this had no significant correlation with disease severity. The present study indicated that elevated circulating PD-1+ T cells can primarily be used as a biomarker for disease diagnosis and a potential therapeutic target.

Keywords: PD-1+CXCR5+ T cells; Tph cells; bronchoalveolar lavage fluid; small cell lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / immunology
  • Bronchoalveolar Lavage Fluid / cytology*
  • Bronchoalveolar Lavage Fluid / immunology
  • Carcinoma, Non-Small-Cell Lung / blood
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Case-Control Studies
  • Female
  • Humans
  • Lung Neoplasms / blood
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / therapy
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Prognosis
  • Programmed Cell Death 1 Receptor / metabolism*
  • Prospective Studies
  • Small Cell Lung Carcinoma / blood
  • Small Cell Lung Carcinoma / diagnosis
  • Small Cell Lung Carcinoma / immunology*
  • Small Cell Lung Carcinoma / therapy
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocyte Subsets / pathology*
  • Tumor Escape / physiology

Substances

  • Biomarkers, Tumor
  • Programmed Cell Death 1 Receptor