Natural killer (NK) cells are innate effector lymphocytes involved in cancer immunosurveillance. Here we investigated the distribution, function and prognosis role of circulating NK cell subsets in non-small cell lung cancer (NSCLC).
Blood samples from 176 NSCLC patients were collected before any treatment and from 41 healthy donors (HD) as control. The phenotype and cytotoxic functions of NK cells were performed by multicolor flow cytometry. Kaplan–Meier method was used to estimate survival.
NSCLC patients exhibited three distinct NK cell subsets in blood such as CD56dim CD16+, CD56dim CD16- and CD56bright NK cells. However, a lower rate of CD56dim CD16+ NK cells and a higher rate of CD56dim CD16- NK cells were found in patients as compared to HD. Unsupervised clustering analysis of activating receptors expression such as NKG2D, NKp30, NKp44, and NKp46 identified four groups of patients with distinct circulating NK cell profiles. We showed that the rate of circulating NKp46+ NK cells was inversely correlated with overall survival (OS). Consistently, the median OS in high versus low level NKp46+ NK cell group was 16 and 27 months respectively (P = 0.04). This effect was mainly driven by NKp46+ CD56dim CD16+ NK cells subset (P = 0.02). Finally, blocking NKp46 receptor in vitro was able to restore antitumor T cell immunity suggesting an inhibitory role of NKp46+ NK cells.
Altogether, our results show a distinct pattern of circulating NK cell subsets in NSCLC and also support the immune regulatory property of NKp46+ NK cell subsets. This study provides important insights on circulating Nkp46+ NK cell subsets as potential prognosis factor in lung cancer.
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Legal entity responsible for the study
Assistance Publique des Hôpitaux de Paris, La Ligue Contre le Cancer, and the Conseil Régional de Franche-Comté.
All authors have declared no conflicts of interest.