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

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

Author information

1
Trinity Translational Medicine Institute, Department of Surgery, Trinity College Dublin, Ireland.
2
Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland.
3
Department of Immunology, Trinity College Dublin, Ireland.
4
Liver Transplant Unit, St. Vincent's University Hospital, Dublin, Ireland.
5
National Esophageal and Gastric Center, St. James's Hospital, Dublin, Ireland.
6
Trinity Translational Medicine Institute, Department of Surgery, Trinity College Dublin, Ireland; National Esophageal and Gastric Center, St. James's Hospital, Dublin, Ireland.
7
Trinity Translational Medicine Institute, Department of Surgery, Trinity College Dublin, Ireland. Electronic address: jlysaght@tcd.ie.

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.

KEYWORDS:

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

PMID:
29339209
DOI:
10.1016/j.canlet.2018.01.039
[Indexed for MEDLINE]

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