A neutrophil response
linked to tumor control in immunotherapy
Summary
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.
摘要
中性粒细胞在实体瘤中聚集，并且其数量与患者不良预后相关。然而，中性粒细胞并不是同质的，在癌症治疗中能够发挥不同的作用。在本研究中，我们探索了中性粒细胞在免疫治疗中的作用，从而控制肿瘤。我们的研究表明，成功的治疗可短时间增加肿瘤中性粒细胞数量。这种增加可能归因于Sellhi状态，而不是加速肿瘤进展的其他中性粒细胞。治疗诱导的中性粒细胞获得了在人类患者中也可见到的干扰素基因标签，并且似乎对于治疗成功至关重要，因为中性粒细胞中干扰素应答转录因子IRF1的缺失导致免疫治疗失败。中性粒细胞应答依赖于抗肿瘤免疫的关键成分，包括BATF3依赖的DCs、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转归呈显著相关性。因此，我们明确了中性粒细胞状态在介导癌症有效治疗方面的关键作用。
参考文献
A neutrophil response linked to tumor control in immunotherapy. Cell, 2023, 186(7), 1448–1464.e20. doi: 10.1016/j.cell.2023.02.032.
