期刊
CANCER IMMUNOLOGY RESEARCH
卷 7, 期 2, 页码 208-218出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2326-6066.CIR-18-0085
关键词
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资金
- l'Institut National du Cancer [PLBIO-2011-6]
- PAIR Melanome [2013-0662013]
- l'Association pour la Recherche contre le Cancer (ARC) [3964]
- la Ligue Nationale contre le Cancer (Comite Ile de France)
- l'Assistance Publique des Hopitaux de Paris (APHP
- DRCD, Immumela program)
- Siric (site de recherche integree sur le cancer)
- Institut Curie
- Ligue Nationale Contre le Cancer
- Canceropole Ile-de-France
- Association Robert Debre pour la Recherche Medicale
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 thorn 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 I-low 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.
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