挪威奥斯陆大学医院Karl-Johan Malmberg、美国西奈山伊坎医学院Amir Horowitz小组，通过转录参考图谱进行肿瘤浸润性自然杀伤细胞的泛癌谱分析。2024年7月2日出版的《自然—免疫学》杂志发表了这项成果。

在本研究中，该研究团队生成了健康人类血液和组织来源的自然杀伤细胞的单细胞转录参考图谱，具有时间分辨率和命运特异性表达的基因调控网络定义自然杀伤细胞分化。迁移学习有助于将肿瘤浸润自然杀伤细胞转录组(39个数据集，7个实体肿瘤，427例患者)纳入参考图谱，以分析肿瘤微环境(TME)诱导的干扰。

在鉴定的六种功能不同的自然杀伤细胞状态中，易受肿瘤微环境诱导的免疫抑制的功能失调应激CD56^bright状态，和细胞毒性肿瘤微环境耐药效应CD56^dim状态，在各种肿瘤类型中都普遍富集，其比例可预测恶性黑色素瘤和骨肉瘤患者的预后。这种资源可以为新的自然杀伤细胞疗法的设计提供信息，并且可以通过迁移学习来扩展，以查询来自实验干扰或疾病条件的新数据集。

据悉，自然杀伤(NK)细胞的功能多样性源于分化、体内平衡、受体-配体相互作用和对病毒感染的适应性反应。

附：英文原文

Title: Pan-cancer profiling of tumor-infiltrating natural killer cells through transcriptional reference mapping

Author: Netskar, Herman, Pfefferle, Aline, Goodridge, Jodie P., Sohlberg, Ebba, Dufva, Olli, Teichmann, Sarah A., Brownlie, Demi, Michalsson, Jakob, Marquardt, Nicole, Clancy, Trevor, Horowitz, Amir, Malmberg, Karl-Johan

Issue&Volume: 2024-07-02

Abstract: The functional diversity of natural killer (NK) cell repertoires stems from differentiation, homeostatic, receptor–ligand interactions and adaptive-like responses to viral infections. In the present study, we generated a single-cell transcriptional reference map of healthy human blood- and tissue-derived NK cells, with temporal resolution and fate-specific expression of gene-regulatory networks defining NK cell differentiation. Transfer learning facilitated incorporation of tumor-infiltrating NK cell transcriptomes (39 datasets, 7 solid tumors, 427 patients) into the reference map to analyze tumor microenvironment (TME)-induced perturbations. Of the six functionally distinct NK cell states identified, a dysfunctional stressed CD56bright state susceptible to TME-induced immunosuppression and a cytotoxic TME-resistant effector CD56dim state were commonly enriched across tumor types, the ratio of which was predictive of patient outcome in malignant melanoma and osteosarcoma. This resource may inform the design of new NK cell therapies and can be extended through transfer learning to interrogate new datasets from experimental perturbations or disease conditions.

DOI: 10.1038/s41590-024-01884-z

Source: https://www.nature.com/articles/s41590-024-01884-z