SAMHD1 expression is a surrogate marker of immune infiltration and determines prognosis after neoadjuvant chemotherapy in early breast cancer

Lucia Gutierrez- Chamorro, Eudald Felip Falgas, Eva María Castella Fernández, Vanesa Quiroga Garcia, Ifeanyi Jude Ezeonwumelu, Laura Angelats, Anna Esteve, Laia Pérez-Roca, Anna Martinez-Cardus, Pedro Luis Fernandez Ruiz, Angélica Ferrando-Díez, Anna Pous, Milana Bergamino Sirven, Beatriz Cirauqui Cirauqui, Margarita Romeo, Iris Teruel Garcia, Ricard Mesia, Bonaventura Clotet, Eva Riveiro-Munõz, Mireia Margeli Vila*Ester Ballana Guix*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review


Purpose: The lack of validated surrogate biomarkers is still an unmet clinical need in the management of early breast cancer cases that do not achieve complete pathological response after neoadjuvant chemotherapy (NACT). Here, we describe and validate the use of SAMHD1 expression as a prognostic biomarker in residual disease in vivo and in vitro. Methods: SAMHD1 expression was evaluated in a clinical cohort of early breast cancer patients with stage II-III treated with NACT. Heterotypic 3D cultures including tumor and immune cells were used to investigate the molecular mechanisms responsible of SAMHD1 depletion through whole transcriptomic profiling, immune infiltration capacity and subsequent delineation of dysregulated immune signaling pathways. Results: SAMHD1 expression was associated to increased risk of recurrence and higher Ki67 levels in post-NACT tumor biopsies of breast cancer patients with residual disease. Survival analysis showed that SAMHD1-expressing tumors presented shorter time-to-progression and overall survival than SAMHD1 negative cases, suggesting that SAMHD1 expression is a relevant prognostic factor in breast cancer. Whole-transcriptomic profiling of SAMHD1-depleted tumors identified downregulation of IL-12 signaling pathway as the molecular mechanism determining breast cancer prognosis. The reduced interleukin signaling upon SAMHD1 depletion induced changes in immune cell infiltration capacity in 3D heterotypic in vitro culture models, confirming the role of the SAMHD1 as a regulator of breast cancer prognosis through the induction of changes in immune response and tumor microenvironment. Conclusion: SAMHD1 expression is a novel prognostic biomarker in early breast cancer that impacts immune-mediated signaling and differentially regulates inflammatory intra-tumoral response.

Original languageEnglish
Number of pages20
JournalCellullar Oncology
Early online dateSept 2023
Publication statusPublished - 4 Sept 2023


  • Immune infiltration
  • SAMHD1
  • TCP1 complex, IL12-family signaling


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