深入了解癌細(xì)胞與免疫細(xì)胞的相互作用特征，有助于癌癥新療法的開發(fā)。不過，既往研究通常著重于原發(fā)腫瘤與其微環(huán)境之間的相互作用，而免疫細(xì)胞對于癌癥轉(zhuǎn)移患者的作用尚不明確。循環(huán)腫瘤細(xì)胞是幾種癌癥轉(zhuǎn)移的前體，并且偶爾被發(fā)現(xiàn)于血液循環(huán)，與非惡性細(xì)胞例如白細(xì)胞存在相關(guān)性。這些循環(huán)腫瘤細(xì)胞相關(guān)白細(xì)胞的特征和功能，以及白細(xì)胞與循環(huán)腫瘤細(xì)胞之間相互作用的分子特征亦不明確。

　　2019年2月6日，全球自然科學(xué)三大旗艦期刊之一、英國《自然》正刊在線發(fā)表瑞士巴塞爾大學(xué)、巴塞爾大學(xué)醫(yī)院、瑞士生物信息研究院、蘇黎世聯(lián)邦理工學(xué)院的研究報告，分離并分析了乳腺癌患者和小鼠模型的循環(huán)腫瘤細(xì)胞相關(guān)白細(xì)胞及其相應(yīng)癌細(xì)胞。

　　首先，該研究通過單細(xì)胞RNA測序表明，對于大多數(shù)病例，循環(huán)腫瘤細(xì)胞與中性白細(xì)胞相關(guān)。

　　隨后，該研究對中性白細(xì)胞相關(guān)循環(huán)腫瘤細(xì)胞的轉(zhuǎn)錄RNA譜與單純循環(huán)腫瘤細(xì)胞的轉(zhuǎn)錄RNA譜進(jìn)行比較，檢測出許多表達(dá)不同的基因，這些基因引起腫瘤細(xì)胞分裂周期不斷循環(huán)，并且?guī)椭[瘤細(xì)胞更有效地繁殖形成轉(zhuǎn)移灶。

　　此外，該研究發(fā)現(xiàn)細(xì)胞與細(xì)胞連接、細(xì)胞因子與受體配對的基因靶點，可以形成循環(huán)腫瘤細(xì)胞與中性白細(xì)胞之間的松散結(jié)合，造成循環(huán)腫瘤細(xì)胞在轉(zhuǎn)移過程中不斷播散和種植。通過基因編輯技術(shù)，可以終止循環(huán)腫瘤細(xì)胞與中性白細(xì)胞的相互作用，結(jié)束循環(huán)腫瘤細(xì)胞的分裂繁殖、播散、種植。

　　因此，該研究結(jié)果表明，中性白細(xì)胞能夠幫助血液循環(huán)里的腫瘤細(xì)胞不斷地分裂繁殖、播散、種植，該相互作用基因靶點為新的乳腺癌靶向療法奠定了基礎(chǔ)。

　　對此，美國紐約冷泉港實驗室、荷蘭癌癥研究院發(fā)表同期述評：相互勾結(jié)幫助癌癥擴散。

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