Expression of classical human leukocyte antigen class I antigens, HLA‐E and HLA‐G, is adversely prognostic in pancreatic cancer patients
Open Access
- 3 June 2020
- journal article
- research article
- Published by Wiley in Cancer Science
- Vol. 111 (8), 3057-3070
- https://doi.org/10.1111/cas.14514
Abstract
The expression of classical HLA class I antigens (HLA‐I) on the surfaces of cancer cells allows cytotoxic T cells to recognize and eliminate these cells. Reduction or loss of HLA‐I is a mechanism of escape from antitumor immunity. The present study aimed to investigate the clinicopathological impacts of HLA‐I and non‐classical HLA‐I antigens expressed on pancreatic ductal adenocarcinoma (PDAC) cells. We performed immunohistochemistry to detect expression of HLA‐I antigens in PDAC using 243 PDAC cases and examined their clinicopathological influences. We also investigated the expression of immune‐related genes to characterize PDAC tumor microenvironments. Lower expression of HLA‐I, found in 33% of PDAC cases, was significantly associated with longer overall survival. Higher expression of both HLA‐E and HLA‐G was significantly associated with shorter survival. Multivariate analyses revealed that higher expression of these three HLA‐I antigens was significantly correlated with shorter survival. Higher HLA‐I expression on PDAC cells was significantly correlated with higher expression of IFNG , which also correlated with PD1 , PD‐L1 , and PD‐L2 expression. In vitro assay revealed that IFNg stimulation increased surface expression of HLA‐I in three PDAC cell lines. It also upregulated surface expression of HLA‐E, HLA‐G, and immune checkpoint molecules including PD‐L1 and PD‐L2. These results suggest that the higher expression of HLA‐I, HLA‐E, and HLA‐G on PDAC cells is an unfavorable prognosticator. It is possible that IFNg promotes a tolerant microenvironment by inducing immune checkpoint molecules in PDAC tissues with higher HLA‐I expression on PDAC cells.Keywords
Funding Information
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Agency for Medical Research and Development
This publication has 49 references indexed in Scilit:
- Arginase II Expressed in Cancer-Associated Fibroblasts Indicates Tissue Hypoxia and Predicts Poor Outcome in Patients with Pancreatic CancerPLOS ONE, 2013
- Establishment of a monoclonal anti‐pan HLA class I antibody suitable for immunostaining of formalin‐fixed tissue: Unusually high frequency of down‐regulation in breast cancer tissuesPathology International, 2012
- HLA-E expression by gynecological cancers restrains tumor-infiltrating CD8+T lymphocytesProceedings of the National Academy of Sciences, 2011
- Tumour necrosis is a postoperative prognostic marker for pancreatic cancer patients with a high interobserver reproducibility in histological evaluationBritish Journal of Cancer, 2010
- Pancreatic CancerNew England Journal of Medicine, 2010
- Human Leukocyte Antigen-G Protein Expression Is an Unfavorable Prognostic Predictor of Hepatocellular Carcinoma following Curative ResectionClinical Cancer Research, 2009
- Clinical impact of HLA class I expression in rectal cancerCancer Immunology, Immunotherapy, 2007
- Tolerization of dendritic cells by HLA‐GEuropean Journal of Immunology, 2005
- Hypoxia — a key regulatory factor in tumour growthNature Reviews Cancer, 2002
- Differential expression of HLA-E, HLA-F, and HLA-G transcripts in human tissueHuman Immunology, 1990