Neutrophils accumulate in solid tumors, and their abundance correlates with poor prognosis. Neutrophils are not homogeneous, however, and could play different roles in cancer therapy. Here, we investigate the role of neutrophils in immunotherapy, leading to tumor control. We show that successful therapies acutely expanded tumor neutrophil numbers. This expansion could be attributed to a Sell^hi state rather than to other neutrophils that accelerate tumor progression. Therapy-elicited neutrophils acquired an interferon gene signature, also seen in human patients, and appeared essential for successful therapy, as loss of the interferon-responsive transcription factor IRF1 in neutrophils led to failure of immunotherapy. The neutrophil response depended on key components of anti-tumor immunity, including BATF3-dependent DCs, IL-12, and IFNγ. In addition, we found that a therapy-elicited systemic neutrophil response positively correlated with disease outcome in lung cancer patients. Thus, we establish a crucial role of a neutrophil state in mediating effective cancer therapy.

中性粒细胞在实体瘤中积聚，其丰度与不良预后相关。然而，中性粒细胞并不均质，并且在癌症治疗中可能发挥不同的作用。在这里，我们研究中性粒细胞在免疫治疗中的作用，从而控制肿瘤。我们表明，成功的治疗可急剧增加肿瘤中性粒细胞的数量。这种扩张可能归因于Sell ^hi状态，而不是加速肿瘤进展的其他中性粒细胞。治疗引发的中性粒细胞获得了干扰素基因特征，这在人类患者中也可见到，并且似乎对于成功治疗至关重要，因为中性粒细胞中干扰素反应性转录因子 IRF1 的缺失会导致免疫治疗失败。中性粒细胞反应取决于抗肿瘤免疫的关键成分，包括 BATF3 依赖性 DC、IL-12 和 IFNγ。此外，我们发现治疗引起的全身中性粒细胞反应与肺癌患者的疾病结果呈正相关。因此，我们确定了中性粒细胞状态在介导有效的癌症治疗中的关键作用。