法国蔚蓝海岸大学Jean Albrengues和Cédric Gaggioli课题组的研究发现，化疗时中性粒细胞产生的细胞外陷阱通过激活TGF-β赋予治疗耐药性。2023年4月10日出版的《癌细胞》发表了这项成果。

研究表明化疗诱导的中性粒细胞招募和中性粒细胞细胞外陷阱（NET），能降低乳腺癌肺转移小鼠模型中小鼠对治疗的反应。研究人员发现化疗治疗的癌细胞分泌IL-1β，进而诱导NET形成。诱导化学耐药性需要两种NET相关蛋白：整合素-αvβ1——其捕获潜在的TGF-β蛋白，和基质金属蛋白酶9——其切割并激活潜在捕获蛋白TGF-β。TGF-β激活的癌细胞会发生上皮到间充质转变，这与化学耐药性相关。

该研究工作表明，NETs通过捕获和激活细胞因子来调节邻近细胞的活性，并表明靶向IL-1β-NET-TGF-β轴可以减少或预防转移肿瘤微环境中的化学耐药性。

据悉，转移是癌症死亡的主要原因，治疗耐药性很常见。肿瘤微环境可以赋予化疗耐药性（化学耐药性），但对特定宿主细胞如何影响治疗效果知之甚少。

附：英文原文

Title: Neutrophil extracellular traps formed during chemotherapy confer treatment resistance via TGF-β activation

Author: Alexandra Mousset, Enora Lecorgne, Isabelle Bourget, Pascal Lopez, Kitti Jenovai, Julien Cherfils-Vicini, Chloé Dominici, Géraldine Rios, Cédric Girard-Riboulleau, Bodu Liu, David L. Spector, Sidse Ehmsen, Shufang Renault, Caroline Hego, Fatima Mechta-Grigoriou, Franois-Clément Bidard, Mikkel Green Terp, Mikala Egeblad, Cédric Gaggioli, Jean Albrengues

Issue&Volume: 2023/04/10

Abstract: Metastasis is the major cause of cancer death, and the development of therapy resistanceis common. The tumor microenvironment can confer chemotherapy resistance (chemoresistance),but little is known about how specific host cells influence therapy outcome. We showthat chemotherapy induces neutrophil recruitment and neutrophil extracellular trap(NET) formation, which reduces therapy response in mouse models of breast cancer lungmetastasis. We reveal that chemotherapy-treated cancer cells secrete IL-1β, whichin turn triggers NET formation. Two NET-associated proteins are required to inducechemoresistance: integrin-αvβ1, which traps latent TGF-β, and matrix metalloproteinase9, which cleaves and activates the trapped latent TGF-β. TGF-β activation causes cancercells to undergo epithelial-to-mesenchymal transition and correlates with chemoresistance.Our work demonstrates that NETs regulate the activities of neighboring cells by trappingand activating cytokines and suggests that chemoresistance in the metastatic settingcan be reduced or prevented by targeting the IL-1β-NET-TGF-β axis.

DOI: 10.1016/j.ccell.2023.03.008

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00081-8