转移是癌症死亡的主要原因，治疗抵抗力的发展很常见。肿瘤微环境可以赋予化疗抵抗力（化疗抵抗力），但是我们很少知道特定宿主细胞如何影响治疗效果。我们显示了化疗诱导中性粒细胞招募和中性粒细胞外泌物（NET）的形成，这减少了乳腺癌肺转移小鼠模型的治疗反应。我们揭示了化疗处理的癌细胞分泌IL-1β，进而触发NET形成。有两种与NET相关的蛋白质需要诱导化疗抵抗力：整合素αvβ1，可捕获潜在的TGF-β，并且基质金属蛋白酶9，可切割和激活捕获的潜在TGF-β。TGF-β激活使癌细胞经历上皮细胞向间充质细胞的转变，并与化疗抵抗相关。我们的工作表明NET通过捕获和激活细胞因子来调节邻近细胞的活动，并且暗示靶向IL-1β-NET-TGF-β轴可以减少或预防转移性环境中的化疗抵抗。版权所有©2023 Elsevier Inc.。保留所有权利。

Metastasis is the major cause of cancer death, and the development of therapy resistance is common. The tumor microenvironment can confer chemotherapy resistance (chemoresistance), but little is known about how specific host cells influence therapy outcome. We show that chemotherapy induces neutrophil recruitment and neutrophil extracellular trap (NET) formation, which reduces therapy response in mouse models of breast cancer lung metastasis. We reveal that chemotherapy-treated cancer cells secrete IL-1β, which in turn triggers NET formation. Two NET-associated proteins are required to induce chemoresistance: integrin-αvβ1, which traps latent TGF-β, and matrix metalloproteinase 9, which cleaves and activates the trapped latent TGF-β. TGF-β activation causes cancer cells to undergo epithelial-to-mesenchymal transition and correlates with chemoresistance. Our work demonstrates that NETs regulate the activities of neighboring cells by trapping and activating cytokines and suggests that chemoresistance in the metastatic setting can be reduced or prevented by targeting the IL-1β-NET-TGF-β axis.Copyright © 2023 Elsevier Inc. All rights reserved.