Highlights
- •Upregulation of HLA-E is associated with improved survival in endometrial cancer (EC).
- •The presence of NK cells predicts survival when HLA-E expression is upregulated.
- •The presence of NK cells is associated with a worse prognosis when HLA-E expression is normal.
- •The prognostic benefit of T cells is not modulated by HLA-E expression in EC.
- •HLA-E may have opposing actions on tumour-infiltrating immune cells in EC.
Abstract
Background
Human Leucocyte Antigen- E (HLA-E) has been reported as both a positive and negative
prognostic marker in cancer. This apparent discrepancy may be due to opposing actions
of HLA-E on tumour-infiltrating immune cells. Therefore, we evaluated HLA-E expression
and survival in relation to the presence of intratumoural natural killer (NK) cells
and cytotoxic T cells (CTLs).
Methods
Tissue microarrays (TMAs) of endometrial tumours were used for immunohistochemical
staining of parameters of interest. The combined impact of clinical, pathological
and immune parameters on survival was analysed using log rank testing and Cox regression
analyses.
Results
Upregulation of HLA-E was associated with an improved disease-free and disease-specific
survival in univariate analysis (HR 0.58 95% CI 0.37–0.89; HR 0.42 95% CI 0.25–0.73,
respectively). In multivariate analysis, the presence of NK cells predicts survival
with a hazard ratio (HR) 0.28 (95% confidence interval (CI) 0.09–0.91) when HLA-E
expression is upregulated; but it is associated with a worse prognosis when HLA-E
expression is normal (HR 13.43, 95% CI 1.70–106.14). By contrast, the prognostic benefit
of T cells was not modulated by HLA-E expression.
Conclusions
Taken together, we demonstrate that the prognostic benefit of NK cells, but not T-cells,
is influenced by HLA-E expression in endometrial cancer (EC) and propose a model to
explain our observations.
Keywords
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Article info
Publication history
Published online: October 20, 2017
Accepted:
September 14,
2017
Received:
April 28,
2017
Identification
Copyright
© 2017 Elsevier Ltd. All rights reserved.
