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Published in: BMC Cancer 1/2009

Open Access 01-12-2009 | Research article

Low NKp30, NKp46 and NKG2D expression and reduced cytotoxic activity on NK cells in cervical cancer and precursor lesions

Authors: Trinidad Garcia-Iglesias, Alicia del Toro-Arreola, Benibelks Albarran-Somoza, Susana del Toro-Arreola, Pedro E Sanchez-Hernandez, Maria Guadalupe Ramirez-Dueñas, Luz Ma. Adriana Balderas-Peña, Alejandro Bravo-Cuellar, Pablo C Ortiz-Lazareno, Adrian Daneri-Navarro

Published in: BMC Cancer | Issue 1/2009

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Abstract

Background

Persistent high risk HPV infection can lead to cervical cancer, the second most common malignant tumor in women worldwide. NK cells play a crucial role against tumors and virus-infected cells through a fine balance between activating and inhibitory receptors. Expression of triggering receptors NKp30, NKp44, NKp46 and NKG2D on NK cells correlates with cytolytic activity against tumor cells, but these receptors have not been studied in cervical cancer and precursor lesions. The aim of the present work was to study NKp30, NKp46, NKG2D, NKp80 and 2B4 expression in NK cells from patients with cervical cancer and precursor lesions, in the context of HPV infection.

Methods

NKp30, NKp46, NKG2D, NKp80 and 2B4 expression was analyzed by flow cytometry on NK cells from 59 patients with cervical cancer and squamous intraepithelial lesions. NK cell cytotoxicity was evaluated in a 4 hour CFSE/7-AAD flow cytometry assay. HPV types were identified by PCR assays.

Results

We report here for the first time that NK cell-activating receptors NKp30 and NKp46 are significantly down-regulated in cervical cancer and high grade squamous intraepithelial lesion (HGSIL) patients. NCRs down-regulation correlated with low cytolytic activity, HPV-16 infection and clinical stage. NKG2D was also down-regulated in cervical cancer patients.

Conclusion

Our results suggest that NKp30, NKp46 and NKG2D down-regulation represent an evasion mechanism associated to low NK cell activity, HPV-16 infection and cervical cancer progression.
Appendix
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Metadata
Title
Low NKp30, NKp46 and NKG2D expression and reduced cytotoxic activity on NK cells in cervical cancer and precursor lesions
Authors
Trinidad Garcia-Iglesias
Alicia del Toro-Arreola
Benibelks Albarran-Somoza
Susana del Toro-Arreola
Pedro E Sanchez-Hernandez
Maria Guadalupe Ramirez-Dueñas
Luz Ma. Adriana Balderas-Peña
Alejandro Bravo-Cuellar
Pablo C Ortiz-Lazareno
Adrian Daneri-Navarro
Publication date
01-12-2009
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2009
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-9-186

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