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深入了解癌细胞与免疫细胞的相互作用特征，有助于癌症新疗法的开发。不过，既往研究通常着重于原发肿瘤与其微环境之间的相互作用，而免疫细胞对于癌症转移患者的作用尚不明确。循环肿瘤细胞是几种癌症转移的前体，并且偶尔被发现于血液循环，与非恶性细胞例如白细胞存在相关性。这些循环肿瘤细胞相关白细胞的特征和功能，以及白细胞与循环肿瘤细胞之间相互作用的分子特征亦不明确。 2019年2月6日，全球自然科学三大旗舰期刊之一、英国《自然》正刊在线发表瑞士巴塞尔大学、巴塞尔大学医院、瑞士生物信息研究院、苏黎世联邦理工学院的研究报告，分离并分析了乳腺癌患者和小鼠模型的循环肿瘤细胞相关白细胞及其相应癌细胞。 首先，该研究通过单细胞RNA测序表明，对于大多数病例，循环肿瘤细胞与中性白细胞相关。 随后，该研究对中性白细胞相关循环肿瘤细胞的转录RNA谱与单纯循环肿瘤细胞的转录RNA谱进行比较，检测出许多表达不同的基因，这些基因引起肿瘤细胞分裂周期不断循环，并且帮助肿瘤细胞更有效地繁殖形成转移灶。 此外，该研究发现细胞与细胞连接、细胞因子与受体配对的基因靶点，可以形成循环肿瘤细胞与中性白细胞之间的松散结合，造成循环肿瘤细胞在转移过程中不断播散和种植。通过基因编辑技术，可以终止循环肿瘤细胞与中性白细胞的相互作用，结束循环肿瘤细胞的分裂繁殖、播散、种植。 因此，该研究结果表明，中性白细胞能够帮助血液循环里的肿瘤细胞不断地分裂繁殖、播散、种植，该相互作用基因靶点为新的乳腺癌靶向疗法奠定了基础。 对此，美国纽约冷泉港实验室、荷兰癌症研究院发表同期述评：相互勾结帮助癌症扩散。 Nature. 2019 Feb 6. [Epub ahead of print] Neutrophils escort circulating tumour cells to enable cell cycle progression. Barbara Maria Szczerba, Francesc Castro-Giner, Marcus Vetter, Ilona Krol, Sofia Gkountela, Julia Landin, Manuel C. Scheidmann, Cinzia Donato, Ramona Scherrer, Jochen Singer, Christian Beisel, Christian Kurzeder, Viola Heinzelmann-Schwarz, Christoph Rochlitz, Walter Paul Weber, Niko Beerenwinkel, Nicola Aceto. University of Basel and University Hospital Basel, Basel, Switzerland; SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland; ETH Zurich, Basel, Switzerland. A better understanding of the features that define the interaction between cancer cells and immune cells is important for the development of new cancer therapies. However, focus is often given to interactions that occur within the primary tumour and its microenvironment, whereas the role of immune cells during cancer dissemination in patients remains largely uncharacterized. Circulating tumour cells (CTCs) are precursors of metastasis in several types of cancer, and are occasionally found within the bloodstream in association with non-malignant cells such as white blood cells (WBCs). The identity and function of these CTC-associated WBCs, as well as the molecular features that define the interaction between WBCs and CTCs, are unknown. Here we isolate and characterize individual CTC-associated WBCs, as well as corresponding cancer cells within each CTC-WBC cluster, from patients with breast cancer and from mouse models. We use single-cell RNA sequencing to show that in the majority of these cases, CTCs were associated with neutrophils. When comparing the transcriptome profiles of CTCs associated with neutrophils against those of CTCs alone, we detect a number of differentially expressed genes that outline cell cycle progression, leading to more efficient metastasis formation. Further, we identify cell-cell junction and cytokine-receptor pairs that define CTC-neutrophil clusters, representing key vulnerabilities of the metastatic process. Thus, the association between neutrophils and CTCs drives cell cycle progression within the bloodstream and expands the metastatic potential of CTCs, providing a rationale for targeting this interaction in treatment of breast cancer. DOI: 10.1038/s41586-019-0915-y Nature. 2019 Feb 6. [Epub ahead of print] Sticking together helps cancer to spread. Mikala Egeblad, Karin E. de Visser. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA. Netherlands Cancer Institute, Amsterdam, the Netherlands. When cancer spreads, this metastatic stage of the disease is usually lethal. An analysis of immune cells that cluster with tumour cells in the bloodstream illuminates a partnership that might aid metastasis. DOI: 10.1038/d41586-019-00341-4
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