美国哈佛大学医学院Mikael J. Pittet等研究人员合作发现一个与免疫疗法中的肿瘤控制有关的中性粒细胞反应。该研究于2023年3月30日发表于国际一流学术期刊《细胞》。
研究人员报道了中性粒细胞在免疫疗法中的作用，从而导致肿瘤的控制。结果表明，成功的治疗方法会急性地扩大肿瘤中性粒细胞的数量。这种扩张可归因于Sellhi状态，而不是其他加速肿瘤进展的中性粒细胞。治疗激发的中性粒细胞获得了干扰素基因特征，这在人类患者中也能看到，而且似乎对成功治疗至关重要，因为中性粒细胞中干扰素反应性转录因子IRF1的丢失导致免疫治疗的失败。中性粒细胞的反应取决于抗肿瘤免疫的关键成分，包括依赖BATF3的DC、IL-12和IFNγ。
此外，研究人员发现，治疗激发的全身性中性粒细胞反应与肺癌患者的疾病结局呈正相关。因此，研究人员确立了中性粒细胞状态在介导有效癌症治疗中的关键作用。
据介绍，中性粒细胞在实体瘤中聚集，它们的数量与预后不良相关。然而，中性粒细胞不是同质的，在癌症治疗中可能发挥不同的作用。
附：英文原文
Title: A neutrophil response linked to tumor control in immunotherapy
Author: Jeremy Gungabeesoon, Nicolas A. Gort-Freitas, Máté Kiss, Evangelia Bolli, Marius Messemaker, Marie Siwicki, Mehdi Hicham, Ruben Bill, Peter Koch, Chiara Cianciaruso, Florent Duval, Christina Pfirschke, Michael Mazzola, Solange Peters, Krisztian Homicsko, Christopher Garris, Ralph Weissleder, Allon M. Klein, Mikael J. Pittet
Issue&Volume: 2023/03/30
Abstract: Neutrophils accumulate in solid tumors, and their abundance correlates with poor prognosis.Neutrophils are not homogeneous, however, and could play different roles in cancertherapy. Here, we investigate the role of neutrophils in immunotherapy, leading totumor control. We show that successful therapies acutely expanded tumor neutrophilnumbers. This expansion could be attributed to a Sellhi state rather than to other neutrophils that accelerate tumor progression. Therapy-elicitedneutrophils acquired an interferon gene signature, also seen in human patients, andappeared essential for successful therapy, as loss of the interferon-responsive transcriptionfactor IRF1 in neutrophils led to failure of immunotherapy. The neutrophil responsedepended on key components of anti-tumor immunity, including BATF3-dependent DCs,IL-12, and IFNγ. In addition, we found that a therapy-elicited systemic neutrophilresponse positively correlated with disease outcome in lung cancer patients. Thus,we establish a crucial role of a neutrophil state in mediating effective cancer therapy.
DOI: 10.1016/j.cell.2023.02.032
Source: https://www.cell.com/cell/fulltext/S0092-8674(23)00210-6