SAMHD1 expression modulates innate immune activation and correlates with ovarian cancer prognosis
Gutiérrez-Chamorro, Lucía (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Felip, Eudald (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Bernat-Peguera, Adrià (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Ezeonwumelu, I.J (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Teruel, Iris (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Martínez Cardús, Anna (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Clotet Sala, Bonaventura (Centro de Investigación Biomédica en Red de Enfermedades Infecciosas)
Riveira-Muñoz, Eva (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Romeo, Margarita (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Margelí, Mireia (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Ballana, Ester (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Universitat Autònoma de Barcelona

Fecha:	2023
Resumen:	SAMHD1 is a deoxynucleotide triphosphate (dNTP) triphosphohydrolase which has been proposed as a putative prognostic factor in haematological cancers and certain solid tumours, although with controversial data. Here, we evaluate SAMHD1 function in ovarian cancer, both in vitro and in ovarian cancer patients. SAMHD1 expression was downregulated in ovarian cancer cell lines OVCAR3 and SKOV3 by RNA interference. Gene and protein expression changes in immune signalling pathways were assessed. SAMHD1 expression in ovarian cancer patients was evaluated by immunohistochemistry and survival analysis was performed according to SAMHD1 expression. SAMHD1 knockdown induced a significant upregulation of proinflammatory cytokines concomitant to increased expression of the main RNA-sensors, MDA5 and RIG-I, and interferon-stimulated genes, supporting the idea that the absence of SAMHD1 promotes innate immune activation in vitro. To assess the contribution of SAMHD1 in ovarian cancer patients, tumours were stratified in SAMHD1-low and SAMHD1-high expressing tumours, resulting in significantly shorter progression free survival (PFS) and overall survival (OS) in SAMHD1-high expression subgroup (p =0. 01 and 0. 04, respectively). SAMHD1 depletion correlates with increased innate immune cell signalling in ovarian cancer cells. In clinical samples, SAMHD1-low expressing tumors showed increased progression free survival and overall survival irrespective of BRCA mutation status. These results point towards SAMHD1 modulation as a new therapeutic strategy, able to enhance innate immune activation directly in tumour cells, leading to improved prognosis in ovarian cancer.
Ayudas:	Instituto de Salud Carlos III PI17/00624 Instituto de Salud Carlos III PI21/00642
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	SAMHD1 ; Ovarian cancer ; RLR (RIG-I like receptors) ; Interferon ; Inflammation
Publicado en:	Frontiers in immunology, Vol. 14 (february 2023) , ISSN 1664-3224

DOI: 10.3389/fimmu.2023.1112761
PMID: 36845138

10 p, 3.7 MB

El registro aparece en las colecciones:
Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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