5-Fluorouracil upregulates cell surface B7-H1 (PD-L1) expression in gastrointestinal cancers

Lauren Van Der Kraak,Lin Zhang,Gaurav Goel,Daniel P Normolle,Christof Kaltenmeier,Michael T Lotze,Gordon J Freeman,Rajeev Dhupar,James D Luketich,Katie S Nason,Krishnaveni Ramanan,Daolin Tang,Jon M Davison

doi:10.1186/s40425-016-0163-8

Lauren Van Der Kraak, Lin Zhang + Show 11 more

Open Access

https://doi.org/10.1186/s40425-016-0163-8

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Abstract

BackgroundResistance to chemotherapy is a major obstacle in the effective treatment of cancer patients. B7-homolog 1, also known as programmed death ligand-1 (PD-L1), is an immunoregulatory protein that is overexpressed...

Highlights

Resistance to chemotherapy is a major obstacle in the effective treatment of cancer patients
B7-homolog 1 (B7-H1) protein is detectable by immunohistochemistry in esophageal adenocarcinoma biopsies We have shown that B7-H1 expression can be induced in a 5-FU dose dependent manner in OE33 cells
We have demonstrated that while B7-H1 expression is low at baseline its expression can be induced in HCT 116 p53+/+, HCT 116 p53−/− and OE33 cells following treatment with 5-FU, the chemotherapy of choice for both advanced colorectal cancer (CRC) and esophageal adenocarcinoma (EAC)

Summary

Introduction

Resistance to chemotherapy is a major obstacle in the effective treatment of cancer patients. B7-homolog 1, known as programmed death ligand-1 (PD-L1), is an immunoregulatory protein that is overexpressed in several human cancers. Methods: HCT 116 p53+/+, HCT 116 p53−/− colorectal cancer (CRC) and OE33 esophageal adenocarcinoma (EAC) cells were treated with increasing doses of 5-FU (0.5 uM, 5 uM, 50 uM, 500 uM) or interferon gamma (IFN-γ, 10 ng/ mL) in culture for 24 h and B7-H1 expression was quantified using flow cytometry and western blot analysis. Results: B7-H1 expression in human HCT 116 p53+/+ and HCT 116 p53−/− CRC cells lines, while low at baseline, can be induced by treatment with 5-FU. OE33 baseline B7-H1 expression exceeded CRC cell maximal expression and could be further increased in a dose dependent manner following 5-FU treatment in the absence of immune cells. While B7-H1 expression was not enhanced in post-treatment esophagectomy specimens, this may be due to the limits of immunohistochemical quantification

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