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

Karen C. Galvin, Melissa J. Conroy, Suzanne L. Doyle, Margaret R. Dunne, Ronan Fahey, Emma Foley, Katie E. O'Sullivan, Derek G. Doherty, Justin G. Geoghegan, Narayanasamy Ravi, Cliona O'Farrelly, John V. Reynolds, Joanne Lysaght

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)230-238
Number of pages9
JournalCancer Letters
Volume418
DOIs
Publication statusPublished - 1 Apr 2018

Keywords

  • Cancer
  • Esophageal adenocarcinoma
  • Immunotherapy
  • Inflammation
  • PD-1
  • T cells

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