Negative prognostic impact of regulatory T cell infiltration in surgically resected esophageal cancer post-radiochemotherapy

Oncotarget. 2015 Aug 28;6(25):20840-50. doi: 10.18632/oncotarget.4428.


Ever accumulating evidence indicates that the long-term effects of radiotherapy and chemotherapy largely depend on the induction (or restoration) of an anticancer immune response. Here, we investigated this paradigm in the context of esophageal carcinomas treated by neo-adjuvant radiochemotherapy, in a cohort encompassing 196 patients. We found that the density of the FOXP3+ regulatory T cell (Treg) infiltrate present in the residual tumor (or its scar) correlated with the pathological response (the less Tregs the more pronounced was the histological response) and predicted cancer-specific survival. In contrast, there was no significant clinical impact of the frequency of CD8+ cytotoxic T cells. At difference with breast or colorectal cancer, a loss-of-function allele of toll like receptor 4 (TLR4) improved cancer-specific survival of patients with esophageal cancer. While a loss-of-function allele of purinergic receptor P2X, ligand-gated ion channel, 7 (P2RX7) failed to affect cancer-specific survival, its presence did correlate with an increase in Treg infiltration. Altogether, these results corroborate the notion that the immunosurveillance seals the fate of patients with esophageal carcinomas treated with conventional radiochemotherapy.

Keywords: ATG16L1; apoptosis; autophagy; immunogenic cell death; pattern recognition receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Apoptosis
  • CD8-Positive T-Lymphocytes / cytology
  • Chemoradiotherapy / methods*
  • Cohort Studies
  • Esophageal Neoplasms / drug therapy
  • Esophageal Neoplasms / immunology*
  • Esophageal Neoplasms / radiotherapy
  • Female
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation, Neoplastic
  • Genotype
  • Humans
  • Immunohistochemistry
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Male
  • Prognosis
  • Receptors, Purinergic P2X7 / metabolism
  • T-Lymphocytes, Regulatory / cytology*
  • Toll-Like Receptor 4 / metabolism
  • Treatment Outcome


  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • P2RX7 protein, human
  • Receptors, Purinergic P2X7
  • TLR4 protein, human
  • Toll-Like Receptor 4