RT Journal Article
SR Electronic
T1 CD16<sup>+</sup>NKG2A<sup>high</sup> Natural Killer Cells Infiltrate Breast Cancer–Draining Lymph Nodes
JF Cancer Immunology Research
JO Cancer Immunol Res
FD American Association for Cancer Research
DO 10.1158/2326-6066.CIR-18-0085
A1 Frazao, Alexandra
A1 Messaoudene, Meriem
A1 Nunez, Nicolas
A1 Dulphy, Nicolas
A1 Roussin, France
A1 Sedlik, Christine
A1 Zitvogel, Laurence
A1 Piaggio, Eliane
A1 Toubert, Antoine
A1 Caignard, Anne
YR 2018
UL http://cancerimmunolres.aacrjournals.org/content/early/2019/01/07/2326-6066.CIR-18-0085.abstract
AB Tumor-draining lymph nodes (TD-LNs) are the first site of metastasis of breast cancer. Natural killer (NK) cells that infiltrate TD-LNs [including noninvaded (NI) or metastatic (M)-LNs from breast cancer patients] and NK cells from healthy donor (HD)-LNs were characterized, and their phenotype analyzed by flow cytometry. Low percentages of tumor cells invaded M-LNs, and these cells expressed ULBP2 and HLA class I molecules. Although NK cells from paired NI and M-LNs were similar, they expressed different markers compared with HD-LN NK cells. Compared with HD-LNs, TD-LN NK cells expressed activating DNAM-1, NKG2C and inhibitory NKG2A receptors, and exhibited elevated CXCR3 expression. CD16, NKG2A, and NKp46 expression were shown to be increased in stage IIIA breast cancer patients. TD-LNs contained a large proportion of activated CD56brightCD16+ NK cells with high expression of NKG2A. We also showed that a subset of LN NK cells expressed PD-1, expression of which was correlated with NKp30 and NKG2C expression. LN NK cell activation status was evaluated by degranulation potential and lytic capacity toward breast cancer cells. NK cells from TD-LNs degranulated after coculture with breast cancer cell lines. Cytokine-activated TD-LN NK cells exerted greater lysis of breast cancer cell lines than HD-LN NK cells and preferentially lysed the HLA class Ilow MCF-7 breast cancer cell line. TD-LNs from breast cancer patients, thus, contained activated lytic NK cells. The expression of inhibitory receptor NKG2A and checkpoint PD-1 by NK cells infiltrating breast cancer–draining LNs supports their potential as targets for immunotherapies using anti-NKG2A and/or anti–PD-1.