Predictive value of peripheral regulatory T cells in non-small cell lung cancer patients undergoing radiotherapy

Oncotarget. 2017 Jun 27;8(26):43427-43438. doi: 10.18632/oncotarget.15238.

Abstract

Background: Studies increasingly focus on the impact of radiotherapy on immunity; however, the role of peripheral cellular immunity prior to radiotherapy in cancer patients remains largely unknown. In this study, we investigated the predictive roles of lymphocyte subsets on tumor progression in non-small cell lung cancer (NSCLC) patients undergoing radiotherapy, and their expression in NSCLC patients at first relapse.

Methods: We enrolled 70 NSCLC patients and 14 age- and sex-matched healthy donors and tested the lymphocyte subsets in their peripheral blood by flow cytometry. Among them, 40 newly diagnosed patients received radiotherapy and were enrolled to investigate the predictive value of lymphocyte subsets on tumor progression after radiotherapy by uni- and multivariate analyses; 30 patients at first relapse were included to evaluate the differences of lymphocyte subsets between them and first diagnosed patients and healthy volunteers.

Results: Increased proportions of regulatory T cells, CD8+ T cells, and CD8+CD28- T cells and decreased CD4+ T cells and CD4/CD8 ratios were observed in NSCLC patients at first relapse compared to newly diagnosed patients. In the 40 first diagnosed patients undergoing radiotherapy, uni- and multivariate analyses showed that increased level of regulatory T cells correlated with poor progression-free survival (hazard ratio = 2.55 and 3.76, P = 0.022 and 0.010, respectively).

Conclusions: Peripheral regulatory T cells were increased and independently predict tumor progression in NSCLC patients undergoing radiotherapy, suggesting the promising combination of radiotherapy and immunotherapy.

Keywords: T cells; immunotherapy; lymphocyte subsets; non-small cell lung cancer; stereotactic body radiation therapy.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / immunology*
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Non-Small-Cell Lung / radiotherapy
  • Combined Modality Therapy
  • Female
  • Flow Cytometry
  • Humans
  • Immunotherapy
  • Kaplan-Meier Estimate
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / radiotherapy
  • Lymphocyte Count
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Predictive Value of Tests
  • Prognosis
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism

Substances

  • Biomarkers