Document Detail

Human anaplastic thyroid carcinoma cells are sensitive to NK cell-mediated lysis via ULBP2/5/6 and chemoattract NK cells.
MedLine Citation:
PMID:  25212604     Owner:  NLM     Status:  Publisher    
Purpose: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive forms of cancer with no curative therapies available. To date, strategies to target ATC by immunotherapy have not been evaluated. We investigated whether ATC would be a suitable target for NK-cell-based immunotherapy. Experimental Design: We first established 7 new cell lines from ATC tumors, 3 from PTC tumors and analyzed them together with 8 additional ATC cell lines. Cells were analyzed for sensitivity to lysis by NK cells and their ability to chemoattract and regulate the activity of NK cells. In addition, fresh tumor samples and peripheral blood from 6 ATC patients were analyzed for NK cell infiltration and phenotype. Results: We observed that ATC cell lines are sensitive to lysis by ex vivo expanded NK cells and that the lysis was abrogated upon blockade of NKG2D. Sensitivity of thyroid cancer cell lines to NK-cell-mediated lysis correlated with surface expression of UL16-binding protein 2 on tumor cells. Moreover, ATC cell lines produced high levels of CXCL10 and stimulated migration of expanded NK cells and ATC tumors were enriched for NK cells expressing the cognate chemokine receptor CXCR3. However, compared with NK cells in peripheral blood, ATC-tumor-derived NK cells displayed a suppressed phenotype with a down-regulated expression of NKG2D. In vitro, suppression of NK-cell-mediated lysis and NKG2D expression by ATC cells was restored upon neutralization of prostaglandin-E2. Conclusions: ATC cell lines are sensitive to NK-cell-mediated lysis via ULBP2/5/6 and chemoattract CXCR3-positive NK-cells. Patients with ATC may benefit from NK-cell-based immunotherapy.
Erik Wennerberg; Aline Pfefferle; Lars Ekblad; Yuya Yoshimoto; Veronika Kremer; Vitaliy O Kaminskyy; C Christofer Juhlin; Anders Hoog; Inger Bodin; Vitalijs Svjatoha; Catharina Larsson; Jan Zedenius; Johan Wennerberg; Andreas Lundqvist
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-9-11
Journal Detail:
Title:  Clinical cancer research : an official journal of the American Association for Cancer Research     Volume:  -     ISSN:  1078-0432     ISO Abbreviation:  Clin. Cancer Res.     Publication Date:  2014 Sep 
Date Detail:
Created Date:  2014-9-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9502500     Medline TA:  Clin Cancer Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014, American Association for Cancer Research.
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