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    
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.
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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