Neutrophils inhibit tumor growth at early stages of tumor formation. (P2006)

Neutrophils are important innate immune cells involved in microbial clearance at sites of infection. However, the roles of neutrophils in cancer development are not clear. We hypothesized that neutrophils might mediate antitumor effects at the initial tumor formation stage. To test this hypothesis, we injected 2x106 mouse lung Lewis cancer cells into the flanks of C57BL/6 and Cxcr2-/- mice, the latter lack the receptor for ELR+ CXC neutrophil chemokines. We observed increased tumor growth in Cxcr2-/- mice as compared with controls within 3 weeks of injection. FACS analysis indicated fewer neutrophils and more IL-17-producing cells in the tumors of Cxcr2-/- mice than those of C57BL/6 mice. We further tested the roles of neutrophils using anti-Ly6G antibody depletion at the time of tumor cell injection. We demonstrated that tumors grew faster in the neutrophil depleted group, while the percentages of IL-17-producing cells in the tumors and the levels of G-CSF in the plasma were also increased in the absence of neutrophils. To test whether neutrophils have a direct cytotoxic effect on LLC cells, we performed in vitro cell killing assays. We demonstrated neutrophils isolated from both circulation and bone marrow exerted cytotoxic effects. In conclusion, by using Cxcr2-/- and neutrophil antibody-depleted C57BL/6 mice, we have demonstrated that initial tumor growth of LLC cells is enhanced in association with inaccessibility of neutrophils and activation of the IL-17/G-CSF axis.