Non-fitness status of peripheral NK cells defined by decreased NKp30 and perforin,and increased soluble B7H6, in cervical cancer patients |
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| Authors: | Gloria Yareli Gutierrez-Silerio Miriam Ruth Bueno-Topete Alejandra Natali Vega-Magaña Blanca Estela Bastidas-Ramirez Jorge Gutierrez-Franco Marta Escarra-Senmarti Eliza Julia Pedraza-Brindis Marcela Peña-Rodriguez Martha Eloisa Ramos-Marquez Vidal Delgado-Rizo Nehla Banu Alan Guillermo Alejandre-Gonzalez Mary Fafutis-Morris Jesse Haramati Susana del Toro-Arreola |
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| Institution: | 1. Instituto de Investigación en Enfermedades Crónico Degenerativas, Departamento de Biología Molecular y Genómica, CUCS, Universidad de Guadalajara, Guadalajara, Mexico;2. Instituto de Investigación en Ciencias Biomédicas, Departamento de Biología Molecular y Genómica, CUCS, Universidad de Guadalajara, Guadalajara, Mexico;3. Unidad Académica de Ciencias Químico Biológicas y Farmacéuticas, Universidad Autónoma de Nayarit, Tepic, Mexico;4. Division of Rheumatology, The Johns Hopkins University, Baltimore, Maryland, USA;5. Departamento Academia de Aparatos y Sistemas I, Unidad Académica de Ciencias de la Salud, Universidad Autónoma de Guadalajara, Guadalajara, Mexico;6. Laboratorio de Diagnóstico de Enfermedades Emergentes y Reemergentes, Departamento de Microbiología y Patología, CUCS, Universidad de Guadalajara, Guadalajara, Mexico;7. Centro de Investigación en Inmunología y Dermatología, Departamento de Fisiología, CUCS, Universidad de Guadalajara, Guadalajara, Mexico;8. Laboratorio de Inmunobiología, Departamento de Biología Celular y Molecular, CUCBA, Universidad de Guadalajara, Guadalajara, Mexico |
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| Abstract: | The NKp30 receptor is one of the three natural cytotoxic receptors reported in NK cells. This receptor is codified by the NCR3 gene, which encodes three isoforms, a consequence of the alternative splicing of exon 4. A greater expression of the three isoforms (A, B, and C), along with low levels of the NKp30 ligand B7H6, has been reported as a positive prognostic factor in different cancer types. Here, in patients with cervical cancer and precursor lesions, we report an altered immune-phenotype, characterized by non-fitness markers, that correlated with increased disease stage, from CIN 1 to FIGO IV. While overall NK cell numbers increased, loss of NKp30+ NK cells, especially in the CD56dim subpopulation, was found. Perforin levels were decreased in these cells. Decreased expression of the NKp30 C isoform and overexpression of soluble B7H6 was found in cervical cancer patients when compared against healthy subjects. PBMCs from healthy subjects downregulated NKp30 isoforms after co-culture with B7H6-expressing tumour cells. Taken together, these findings describe a unique down-modulation or non-fitness status of the immune response in cervical cancer, the understanding of which will be important for the design of novel immunotherapies against this disease. |
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| Keywords: | B7H6 cervical cancer exhausted NK cells isoforms NCR3 NKp30 NKp30A NKp30B NKp30C |
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