SAMHD1 expression modulates innate immune activation and correlates with ovarian cancer prognosis

Lucía Gutiérrez-Chamorro, Eudald Felip, Adrià Bernat-Peguera, Ifeanyi Jude Ezeonwumelu, Iris Teruel, Anna Martínez-Cardús, Bonaventura Clotet, Eva Riveira-Muñoz, Margarita Romeo, Mireia Margelí*, Ester Ballana*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review


Purpose: 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. Methods: 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. Results: 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). Conclusions: 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.

Original languageEnglish
Article number1112761
Number of pages10
JournalFrontiers in immunology
Publication statusE-pub ahead of print - 9 Feb 2023


  • Humans
  • Female
  • SAM Domain and HD Domain-Containing Protein 1/genetics
  • Apoptosis
  • Ovarian Neoplasms/genetics
  • Cell Line, Tumor
  • Prognosis
  • Immunity, Innate
  • ovarian cancer
  • RLR (RIG-I like receptors)
  • interferon
  • SAMHD1
  • inflammation


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