Circulating NKp46 Natural Killer cells have a potential regulatory property and predict distinct survival in Non-Small Cell Lung Cancer.

Fiche publication

Date publication

janvier 2019

Journal

Oncoimmunology

Auteurs

Membres identifiés du Cancéropôle Est :
Pr ADOTEVI Olivier , Pr BORG Christophe , Dr GODET Yann , Mme JACQUIN Marion , Pr WESTEEL Virginie , Mme LAHEURTE Caroline , Dr GALAINE Jeanne , Dr LOYON Romain

Tous les auteurs :
Picard E, Godet Y, Laheurte C, Dosset M, Galaine J, Beziaud L, Loyon R, Boullerot L, Lauret Marie Joseph E, Spehner L, Jacquin M, Eberst G, Gaugler B, Le Pimpec-Barthes F, Fabre E, Westeel V, Caignard A, Borg C, Adotévi O

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/30713781

Résumé

Natural killer (NK) cells are innate effector lymphocytes widely involved in cancer immunosurveillance. In this study, we described three circulating NK cell subsets in patients with non-small cell lung cancer (NSCLC). Compared to healthy donors (HD), lower rate of the cytotoxic CD56 CD16 NK cells was found in NSCLC patients (76.1% vs 82.4%, = 0.0041). In contrast, the rate of CD56 NK cells was similar between patients and HD. We showed in NSCLC patients a higher rate of a NK cell subset with CD56 CD16 phenotype (16.7% vs 9.9% = 0.0001). The degranulation property and cytokines production were mainly drive by CD56 CD16 NK cell subset in patients. Analysis of natural cytotoxicity receptors (NCRs) expression identified four distinct clusters of patients with distinct NK cell subset profiles as compared to one major cluster in HD. Notably the cluster characterized by a low circulating level of NKp46 NK cell subsets was absent in HD. We showed that the rate of circulating NKp46 CD56 CD16 NK cells influenced the patients' survival. Indeed, the median overall survival in patients exhibiting high versus low level of this NK cell subset was 16 and 27 months respectively (= 0.02). Finally, we demonstrated that blocking NKp46 receptor was able to restore spontaneous tumor specific T cell responses in NSCLC patients. In conclusion, this study showed a distinct distribution and phenotype of circulating NK cell subsets in NSCLC. It also supports the regulatory role of NKp46 NK cell subset in NSCLC patients.