Open Access Highly Accessed Research article

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

Trinidad Garcia-Iglesias1, Alicia del Toro-Arreola1, Benibelks Albarran-Somoza1, Susana del Toro-Arreola1, Pedro E Sanchez-Hernandez1, Maria Guadalupe Ramirez-Dueñas1, Luz Ma. Adriana Balderas-Peña2, Alejandro Bravo-Cuellar3, Pablo C Ortiz-Lazareno3 and Adrian Daneri-Navarro1*

Author Affiliations

1 Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada No 950, Colonia Independencia, Guadalajara, Jalisco, CP 44340, Mexico

2 UMAE Hospital de Especialidades, Centro Medico Nacional de Occidente, Instituto Mexicano del Seguro Social, Mexico

3 Centro de Investigacion Biomedica de Occidente, Instituto Mexicano del Seguro Social, Mexico

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BMC Cancer 2009, 9:186  doi:10.1186/1471-2407-9-186

Published: 16 June 2009

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.