Research Papers:

Highly effective NK cells are associated with good prognosis in patients with metastatic prostate cancer

Christine Pasero, Gwenaëlle Gravis, Samuel Granjeaud, Mathilde Guerin, Jeanne Thomassin-Piana, Palma Rocchi, Naji Salem, Jochen Walz, Alessandro Moretta and Daniel Olive _

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Oncotarget. 2015; 6:14360-14373. https://doi.org/10.18632/oncotarget.3965

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Christine Pasero1,3, Gwenaëlle Gravis3, Samuel Granjeaud1,3, Mathilde Guerin1,3, Jeanne Thomassin-Piana3, Palma Rocchi1,3, Naji Salem3, Jochen Walz3, Alessandro Moretta4 and Daniel Olive1,2,3

1 Centre de Recherche en Cancérologie de Marseille, Inserm, Marseille, France

2 Aix Marseille Université, Marseille, France

3 Institut Paoli-Calmettes, Marseille, France

4 Dipartimento di Medicina Sperimentale (D.I.ME.S.), Università di Genova, Genova, Italy

Correspondence to:

Daniel Olive, email:

Christine Pasero, email:

Keywords: natural killer cells, prostate cancer, metastases, survival, castration resistance

Received: December 21, 2014 Accepted: April 10, 2015 Published: April 29, 2015


Clinical outcome of patients with metastatic prostate cancer (mPC) at diagnosis is heterogeneous and unpredictable; thus alternative treatments such as immunotherapy are investigated. We retrospectively analyzed natural killer (NK) cells by flow cytometry in peripheral blood from 39 mPC patients, with 5 year-follow-up, and their correlation with time to castration resistance (TCR) and overall survival (OS). In parallel, NK functionality was carried out against prostate tumor cell lines, analyzed for the expression of NK cell ligands, to identify the receptors involved in PC recognition. NK cells from patients with longer TCR and OS displayed high expression of activating receptors and high cytotoxicity. The activating receptors NKp30 and NKp46 were the most obvious predictive markers of OS and TCR in a larger cohort of mPC patients (OS: p= 0.0018 and 0.0009; TCR: p= 0.007 and < 0.0001 respectively, log-rank test). Importantly, blocking experiments revealed that NKp46, along with NKG2D and DNAM-1 and, to a lesser extent NKp30, were involved in prostate tumor recognition by NK cells. These results identify NK cells as potential predictive biomarkers to stratify patients who are likely to have longer castration response, and pave the way to explore therapies aimed at enhancing NK cells in mPC patients.

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