MDSC subtypes and CD39 expression on CD8+ T cells predict the efficacy of anti-PD-1 immunotherapy in patients with advanced NSCLC

Eur J Immunol. 2020 Nov;50(11):1810-1819. doi: 10.1002/eji.202048534. Epub 2020 Jul 9.

Abstract

The major suppressive immune cells in tumor sites are myeloid derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and Treg cells, and the major roles of these suppressive immune cells include hindering T-cell activities and supporting tumor progression and survival. In this study, we analyzed the pattern of circulating MDSC subtypes in patients with non-small cell lung cancer (NSCLC) whether those suppressive immune cells hinder T-cell activities leading to poor clinical outcomes. First, we verified PMN-MDSCs, monocytic-MDSCs (M-MDSCs), and Treg cells increased according to the stages of NSCLC, and MDSCs effectively suppressed T-cell activities and induced T-cell exhaustion. The analysis of NSCLC patients treated with anti-PD-1 immunotherapy demonstrated that low PMN-MDSCs, M-MDSCs, and CD39+ CD8+ T cells as an individual and all together were associated with longer progression free survival and overall survival, suggesting PMN-MDSCs, M-MDSCs, and CD39+ CD8+ T cells frequencies in peripheral blood might be useful as potential predictive and prognostic biomarkers.

Keywords: CD39; IL-10; Immune checkpoint inhibitor; MDSC; Non-small cell lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / immunology*
  • Apyrase / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Carcinoma, Non-Small-Cell Lung / immunology*
  • Female
  • Humans
  • Immunotherapy / methods
  • Lung Neoplasms / immunology*
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Myeloid-Derived Suppressor Cells / immunology*
  • Programmed Cell Death 1 Receptor / immunology*

Substances

  • Antigens, CD
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Apyrase
  • CD39 antigen