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中性粒细胞分析揭示了抗瘤抗原的作用

Yingcheng Wu ¹, Jiaqiang Ma ¹, Xupeng Yang ²

¹Department of Liver Surgery and Transplantation and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China; The Center for Microbes, Development and Health, Key Laboratory of Immune Response and Immunotherapy, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai 200031, China.
²Department of Liver Surgery and Transplantation and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
³Center for Molecular Medicine, Children's Hospital of Fudan University and Shanghai Key Laboratory of Medical Epigenetics, International Laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
⁴Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University School of Medicine, Shanghai 200123, China.
⁵The Center for Microbes, Development and Health, Key Laboratory of Immune Response and Immunotherapy, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai 200031, China.
⁶Department of Pathogenic Biology and Basic Medical Research Center, School of Medicine, Nantong University, Nantong 226001, China.
⁷Department of Liver Surgery and Transplantation and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200433, China.

⁰Department of Liver Surgery and Transplantation and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China; The Center for Microbes, Development and Health, Key Laboratory of Immune Response and Immunotherapy, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai 200031, China.

Cell +

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2024年三月6日

在PubMed上查看摘要

概括

中性粒细胞具有不同的抗癌作用,包括抗原呈现,与更好的生存相关. 素代谢和基因组修饰可以增强这种作用,改善抗PD-1治疗等癌症疗法.

科学领域

免疫学
癌症生物学
细胞生物学

背景情况

中性粒细胞是癌症中的关键免疫细胞.
它们的短寿命使得研究它们在瘤中的特定功能变得复杂.
了解中性粒细胞的可塑性对于癌症免疫治疗至关重要.

研究的目的

研究各种癌症类型中中性粒细胞的异质性和功能状态.
在瘤微环境中确定调节中性粒细胞功能的机制.
探索针对中性粒细胞的治疗策略以改善癌症治疗.

主要方法

来自17种癌症类型的单细胞RNA测序 (225个样本).
整合转录基因数据以识别不同的中性粒细胞状态.
在中性粒细胞中分析白代谢和基因素修饰 (H3K27ac).
在小鼠癌症模型中评估基于中性粒细胞的疗法和饮食干预措施.

主要成果

鉴定了10种不同的中性粒细胞状态,包括炎症,血管生成和抗原呈现.
在大多数癌症中,抗原呈现性中性粒细胞计划与改善的患者存活率相关.
鉴定出白代谢和H3K27ac的修饰是抗原呈现的关键调节剂.
在临床前模型中,提供中性粒细胞或素补充剂增强了抗PD-1疗法的有效性.

结论

中性粒细胞在癌症微环境中表现出显著的功能多样性和可塑性.
呈抗原的中性粒细胞是一个有前途的治疗点.
通过白代谢或细胞输送调节中性粒细胞功能,为改善癌症免疫疗法提供了潜在的策略.

关键词:

抗原呈现免疫疗法新抗原胰腺癌分析单细胞RNA测序与瘤相关的中性粒细胞