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2016 ; 5
(1
): e1061175
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CD11b+Ly6G+ cells inhibit tumor growth by suppressing IL-17 production at early
stages of tumorigenesis
#MMPMID26942073
Liu Y
; O'Leary CE
; Wang LS
; Bhatti TR
; Dai N
; Kapoor V
; Liu P
; Mei J
; Guo L
; Oliver PM
; Albelda SM
; Worthen GS
Oncoimmunology
2016[]; 5
(1
): e1061175
PMID26942073
show ga
Neutrophils are important innate immune cells involved in microbial clearance at
the sites of infection. However, their role in cancer development is unclear. We
hypothesized that neutrophils mediate antitumor effects in early tumorigenesis.
To test this, we first studied the cytotoxic effects of neutrophils in vitro.
Neutrophils were cytotoxic against tumor cells, with neutrophils isolated from
tumor-bearing mice trending to have increased cytotoxic activities. We then
injected an ELR+ CXC chemokine-producing tumor cell line into C57BL/6 and
Cxcr2-/- mice, the latter lacking the receptors for neutrophil chemokines. We
observed increased tumor growth in Cxcr2-/- mice. As expected, tumors from
Cxcr2-/- mice contained fewer neutrophils. Surprisingly, these tumors also
contained fewer CD8(+) T cells, but more IL-17-producing cells. Replenishment of
functional neutrophils was correlated with decreased IL-17-producing cells,
increased CD8(+) T cells, and decreased tumor size in Cxcr2-/- mice, while
depletion of neutrophils in C57BL/6 mice showed the opposite effects. Results
from a non-ELR+ CXC chemokine producing tumor further supported that functional
neutrophils indirectly mediate tumor control by suppressing IL-17A production. We
further studied the correlation of IL-17A and CD8(+) T cells in vitro. IL-17A
suppressed proliferation and IFN? production of CD8(+) T cells, while CD11b+Ly6G+
neutrophils did not suppress CD8(+) T cell function. Taken together, these data
demonstrate that, while neutrophils could control tumor growth by direct
cytotoxic effects, the primary mechanism by which neutrophils exert antitumor
effects is to regulate IL-17 production, through which they indirectly promote
CD8(+) T cell responses.
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