慢性髓细胞白血病（CML）是一种血液肿瘤，与骨髓（BM）和外周血（PB）中髓系细胞过度生长有关，其特征为BCR-ABL1易位。鉴于已知CML癌性微环境中的细胞因子受损，我们研究了这种微环境调节对先天淋巴细胞（ILCs）的影响，其在癌症中的作用最近被发现。根据转录基因和细胞因子分泌的特性，确定了三个ILC亚群。我们观察到CML患者血清中IL-18和VEGF-A上升，并且CML PB和BM中富集了ILC2。我们发现IL-18促进ILC2增殖，而CML ILC2高表达CXCR4和CXCR7 BM归巢受体，这可能解释了它们在PB和BM中的富集。接下来，我们发现ILC2通过肿瘤来源的VEGF-A依赖机制被过度激活，从而导致更高的IL-13分泌。在IL-13的作用下，白血病细胞增加其克隆性能力。最后，我们发现与VEGF-A、IL-18和ILC2相关的促瘤因子轴在酪氨酸激酶抑制剂（TKIs）治疗后被破坏，恢复了对疗法有反应的CML患者中所有这些参与者的水平。总的来说，我们的研究揭示了ILC2在CML进展中的作用，介导了VEGF-A和IL-18。

Chronic Myeloid Leukemia (CML) is a hematologic malignancy associated to an unregulated growth of myeloid cells in Bone Marrow (BM) and Peripheral Blood (PB), characterized by the BCR-ABL1 translocation. Given the known cytokine impairment in the leukemic niche of CML, we investigated the impact of this microenvironmental dysregulation on Innate Lymphoid Cells (ILCs), whose role in cancer has recently emerged. Three ILC subsets are identified based on transcriptional profiles and cytokine secretion. We observed that IL-18 and VEGF-A are increased in CML patients' sera and that ILC2s are enriched in CML PB and BM. We found that IL-18 drives ILC2 proliferation and that CML ILC2s highly express CXCR4 and CXCR7 BM-homing receptors, potentially explaining their enrichment in PB and BM, respectively. Next, we showed that ILC2s are hyper-activated through a tumor-derived VEGF-A-dependent mechanism, which leads to higher IL-13 secretion. In response to IL-13, leukemic cells increase their clonogenic capacity. Finally, we discovered that the pro-tumoral axis involving VEGF-A, IL-18 and ILC2s was disrupted upon Tyrosine Kinase Inhibitors' (TKIs) treatment, normalizing the levels of all these players in CML patients responding to therapy. Overall, our study uncovers the involvement of ILC2s in CML progression, mediated by VEGF-A and IL-18.