Document Detail


Alterations in classical and non-classical HLA expression in recurrent and progressive HPV induced vulvar intraepithelial neoplasia (uVIN) and implications for immunotherapy.
MedLine Citation:
PMID:  24415578     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Immunotherapy of uVIN is promising however many patients still fail to show clinical responses, which could be explained by an immune escape through alterations in HLA expression. Therefore, we analysed a cohort of patients with a primary (n=43) and subsequent recurrent uVIN lesion (n=20), vaccine treated uVIN patients (n=12), patients with HPV-induced vulvar carcinoma (n=21) and healthy controls (n=26) for the expression of classical HLA-class I/II and non-classical HLA-E/-G and MICA. HLA-class I was downregulated in 70% of uVIN patients, including patients with a clinical response to immunotherapy. Downregulation of HLA-class I is probably reversible, as only 15% of the uVIN cases displayed loss of heterozygosity (LOH) and HLA-class I could be upregulated in uVIN keratinocyte cultures by IFNγ. HLA-class I downregulation is more frequently associated with LOH in vulvar carcinomas (25-55.5%). HLA-class II was found to be focally expressed in 65% of uVIN patients. Of the non-classical molecules, MICA was downregulated in 80% of uVIN whereas HLA-E and -G were expressed in a minority of cases. Their expression was more prominent in vulvar carcinoma. No differences were found between the alterations observed in paired primary and recurrent uVIN. Importantly downregulation of HLA-B/C in primary uVIN lesions was associated with the development of recurrences and progression to cancer. We conclude that downregulation of HLA is frequently observed in premalignant HPV-induced lesions, including clinical responders to immunotherapy, and is associated with worse clinical outcome. However, in the majority of cases downregulation may still be reversible. © 2014 Wiley Periodicals, Inc.
Authors:
E M G van Esch; B Tummers; V Baartmans; E M Osse; N Ter Haar; M D Trietsch; B W J Hellebrekers; C A G Holleboom; H T C Nagel; L T Tan; G J Fleuren; M I E van Poelgeest; S H van der Burg; E S Jordanova
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-1-10
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  -     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2014 Jan 
Date Detail:
Created Date:  2014-1-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014 UICC.
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