Neutrophils recruit regulatory T-cells into tumors via secretion of CCL17 - A new mechanism of impaired antitumor immunity

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. What's new? Getting rid of tumor associated neutrophils (TANs) can slow tumor growth, but how? This study explored whether TANs help protect tumors by pulling in regulatory T cells. These cells prevent the immune system from attacking the body's own cells; they suppress an immune response, and sometimes infiltrate tumors. In mice, the authors discovered, TANs secrete a chemokine that summons the T-reg cells. The farther along in tumor development, the stronger the attraction. These results show for the first time a link between TANs and T-regs acting together to impair anti-tumor immunity, promoting tumor growth.