中性粒细胞在实体瘤中堆积，其丰度与不良预后相关。然而，中性粒细胞并不是同质的，在癌症治疗中可能发挥不同的作用。在这里，我们研究了中性粒细胞在免疫疗法中的作用，以实现肿瘤控制。我们表明，成功的治疗使肿瘤中性粒细胞数量急剧扩张。这种扩张可以归因于Sellhi状态，而不是加速肿瘤进展的其他中性粒细胞。治疗引起的中性粒细胞获得了干扰素基因签名，也在人类患者中观察到，并且似乎对成功的治疗至关重要，因为中性粒细胞中干扰素反应转录因子IRF1的丧失导致免疫疗法失败。中性粒细胞的反应取决于抗肿瘤免疫中的关键成分，包括BATF3依赖性DC、IL-12和IFNγ。此外，我们发现，治疗引起的系统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癌症治疗中的至关重要作用。版权所有©2023 Elsevier Inc.。保留所有权利。

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 Sellhi 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.Copyright © 2023 Elsevier Inc. All rights reserved.