Tumour Immunology Neutrophil Plasticity

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tumOuR ImmuNOLOGy Neutrophil plasticity

New research published in Cancer example by allowing the activation of of oxygen radicals. Moreover, the Cell suggests that tumour-associated CD8+ T cells and macrophages. The phenotype of neutrophils from SM16- neutrophils can have antitumorigenic finding by Fridlender et al. that large treated tumours was consistent with (‘N1’) or protumorigenic (‘N2’) numbers of neutrophils infiltrate the immuno stimulatory activity, such as functions, a plasticity that has been tumours of mice treated with lower levels of arginase (an immuno- well described for M1 and M2 macro- the TGFβ blocker SM16 led to the suppressant) and higher levels of phage subsets. It is suggested that suggestion that neutrophils are also tumour necrosis factor (an immune the presence of transforming growth involved in the antitumour effects stimulator) than neutrophils from factor-β (TGFβ) in the tumour micro- of TGFβ blockade. Neutrophils untreated tumours. environment prevents the generation accumulated in the tumours of Finally, the authors showed that of N1 neutrophils and that overriding SM16-treated mice in response to depletion of neutrophils in untreated this inhibition by blockade of TGFβ increased production of chemo- mice led to increased CD8+ T cell contributes to the known antitumour attractants, probably produced by activation and decreased tumour effects of TGFβ blockers. tumour-associated macrophages, growth. By contrast, depletion of Blockade of the immuno- and increased expression of adhesion neutrophils from SM16-treated mice suppressive cytokine TGFβ inhibits molecules that support neutrophil decreased SM16-induced CD8+ T cell tumour growth in several ways, for recruitment. Depletion of the infil- activation and antitumour effects, trating neutrophils using a neutrophil- which supports the idea that during specific antibody in SM16-treated TGFβ inhibition neutrophils assume mice significantly reduced the anti- a tumour-cytotoxic N1 phenotype tumour effect of SM16, suggesting and support CD8+ T cell activation that tumour-associated neutrophils to inhibit tumour development. in SM16-treated animals have More work will be required to antitumoral activity. determine to what extent this neutro- Further analysis indicated that only phil plasticity mirrors macrophage tumour-associated neutrophils iso- plasticity. lated from SM16-treated mice — not Lucy Bird neutrophils from untreated mice —

could directly kill tumour cells in vitro, ORIGINAL RESEARCH PAPER Fridlender, Z. G. possibly as a result of increased et al. Polarization of tumor-associated neutrophil expression of the death receptor phenotype by TGF-β: ‘’N1’’ versus ‘’N2’’ TAN. Cancer Cell 16, 183–194 (2009) CD95 and increased production