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BMC Cancer
Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

Prognostic value of HLA class I, HLA-E, HLA-G and Tregs in rectal cancer: a retrospective cohort study

Authors: Marlies S Reimers, Charla C Engels, Hein Putter, Hans Morreau, Gerrit Jan Liefers, Cornelis JH van de Velde, Peter JK Kuppen

Published in: BMC Cancer | Issue 1/2014

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Abstract

Background

Evasion of immune surveillance and suppression of the immune system are important hallmarks of tumorigenesis. The goal of this study was to establish distinct patterns that reflect a rectal tumors’ immune-phenotype and to determine their relation to patient outcome.

Methods

The study population consisted of 495 Stage I-IV non-preoperatively treated rectal cancer patients of which a tissue micro array (TMA) was available. Sections of this TMA were immunohistochemically stained and quantified for presence of Foxp3+ cells (Tregs) and tumor expression of HLA Class I and non-classical HLA-E and HLA-G. All markers were, separate and combined, analyzed for clinical prognostic value.

Results

Expression of HLA class I (DFS HR 0.637 (0.458-0.886), p = 0.013), Foxp3+ infiltration above median (OS HR 0.637 (0.500-0.813), p < 0.001 and DFS HR 0.624 (0.491-0.793), p < 0.001) and expression of HLA-G (DFS HR 0.753 (0.574-0.989), p = 0.042) were related to a better clinical prognosis. When these markers were combined, patients with 2 or 3 markers associated with poor prognosis (loss of HLA Class I, Foxp3+ below median, and weak HLA-G expression), showed a significantly worse survival (OS and DFS p < 0.001). This immune-phenotype was an independent predictor for DFS (HR 1.56 (1.14-2.14), p = 0.019).

Conclusions

In conclusion, rectal tumors showing loss of HLA class I expression, Foxp3+ infiltration below median and weak HLA-G expression were related to a worse OS and DFS. Combining these immune markers lead to the creation of tumor immune-phenotypes , which related to patient outcome and were significant independent clinical prognostic markers in rectal cancer.
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Metadata
Title
Prognostic value of HLA class I, HLA-E, HLA-G and Tregs in rectal cancer: a retrospective cohort study
Authors
Marlies S Reimers
Charla C Engels
Hein Putter
Hans Morreau
Gerrit Jan Liefers
Cornelis JH van de Velde
Peter JK Kuppen
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-486

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