Circulating NKp46+ Natural Killer cells have a potential regulatory property and predict distinct survival in Non-Small Cell Lung Cancer
Autor: | Elodie Lauret Marie Joseph, Laura Boullerot, Françoise Le Pimpec-Barthes, Caroline Laheurte, Emilie Picard, Olivier Adotevi, Laurent Beziaud, Magalie Dosset, Jeanne Galaine, Christophe Borg, Virginie Westeel, Marion Jacquin, Béatrice Gaugler, Elizabeth Fabre, Romain Loyon, Laurie Spehner, Yann Godet, Guillaume Eberst, Anne Caignard |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
lcsh:Immunologic diseases. Allergy Immunology Biology CD16 lcsh:RC254-282 cd16 03 medical and health sciences nsclc nkp46 0302 clinical medicine medicine Immunology and Allergy Cytotoxic T cell Cytotoxicity Receptor Lung cancer nk cells Degranulation Cancer medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Immunosurveillance 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research prognosis lcsh:RC581-607 |
Zdroj: | OncoImmunology, Vol 8, Iss 2 (2019) |
Popis: | 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 CD56dim CD16+ NK cells was found in NSCLC patients (76.1% vs 82.4%, P = 0.0041). In contrast, the rate of CD56bright NK cells was similar between patients and HD. We showed in NSCLC patients a higher rate of a NK cell subset with CD56dim CD16− phenotype (16.7% vs 9.9% P = 0.0001). The degranulation property and cytokines production were mainly drive by CD56dim 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+ CD56dim 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 (P = 0.02). Finally, we demonstrated that blocking NKp46 receptor in vitro 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. |
Databáze: | OpenAIRE |
Externí odkaz: |