期刊
INTERNATIONAL JOURNAL OF CANCER
卷 135, 期 5, 页码 1178-1186出版社
WILEY
DOI: 10.1002/ijc.28770
关键词
tumor-associated neutrophils; regulatory T-cells; CCL17; tumor immunology; immune avoidance
类别
资金
- Israel Cancer Research Fund (Research Career Development Award) [2011-721]
- Chief Scientist of the Israel Ministry of Health [10192]
- Israel Lung Association
The mechanisms by which tumor-associated neutrophils (TANs) affect tumor growth are to a large extent unknown. Regulatory T-cells (T-regs) are functionally immune-suppressive subsets of T-cells. Depletion or inhibition of T-regs can enhance antitumor immunity. We demonstrated both by RT-PCR and by ELISA that murine TANs secrete significant amounts of the T-regs chemoattractant, CCL17, much more than circulating or splenic neutrophils, and at a level progressively increasing during tumor development. Migration assays, both in vitro and in vivo, showed recruitment of T-regs by TANs, which was inhibited with anti-CCL17 monoclonal antibodies. Systemic neutrophil depletion in tumor-bearing mice using anti-Ly6G monoclonal antibodies reduced the migration of T-regs into the tumors. We further showed, using flow cytometry, that CCL17 secretion by TANs is not limited to mouse models of cancer but is also relevant to human TANs. Our results suggest a new indirect mechanism by which TANs may inhibit antitumor immune activity, thus promoting tumor growth. We further describe, for the first time, a clear link between TANs and T-regs acting together to impair antitumor immunity.
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