Extratumoral PD-1 blockade does not perpetuate obesity-associated inflammation in esophageal adenocarcinoma

Cancer Lett. 2018 Apr 1;418:230-238. doi: 10.1016/j.canlet.2018.01.039. Epub 2018 Jan 12.


Checkpoint inhibitors, such as anti-PD-1 (Programmed death-1), are transforming cancer treatment for inoperable or advanced disease. As the incidence of obesity-associated malignancies, including esophageal adenocarcinoma (EAC) continues to increase and treatment with checkpoint inhibitors are being FDA approved for a broader range of cancers, it is important to assess how anti-PD-1 treatment might exacerbate pre-existing inflammatory processes at other sites. Outside the EAC tumor, the omentum and liver were found to be enriched with substantial populations of PD-1 expressing T cells. Treatment of omental and hepatic T cells with anti-PD-1 (clone EH12.2H7) did not enhance inflammatory cytokine expression or proliferation, but transiently increased CD107a expression by CD8+ T cells. Importantly, PD-1-expressing T cells are significantly lower in EAC tumor post neoadjuvant chemoradiotherapy, suggesting that combination with specific conventional treatments may severely impair the efficacy of anti-PD-1 immunotherapy. This study provides evidence that systemically administered anti-PD-1 treatment is unlikely to exacerbate pre-existing T cell-mediated inflammation outside the tumor in obesity-associated cancers, such as EAC. Furthermore, our data suggests that studies are required to identify the negative impact of concomitant therapies on PD-1 expression in order to boost overall response rates.

Keywords: Cancer; Esophageal adenocarcinoma; Immunotherapy; Inflammation; PD-1; T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / complications
  • Adenocarcinoma / immunology*
  • Adenocarcinoma / therapy
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use
  • Chemoradiotherapy
  • Esophageal Neoplasms / complications
  • Esophageal Neoplasms / immunology*
  • Esophageal Neoplasms / therapy
  • Female
  • Humans
  • Inflammation / complications
  • Inflammation / immunology*
  • Inflammation / prevention & control
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Obesity / complications
  • Obesity / immunology*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / immunology*
  • Programmed Cell Death 1 Receptor / metabolism
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism


  • Antibodies, Monoclonal
  • Programmed Cell Death 1 Receptor