残留白血病细胞的免疫控制被认为发生在慢性粒细胞白血病 (CML) 患者中，这些患者在酪氨酸激酶抑制剂 (TKI) 停药后仍维持无治疗缓解 (TFR)。为了研究这一点，我们分析了来自 CML 患者 (n = 13，N = 25)、其他癌症 (n = 28) 和健康患者的 55 个单细胞 RNA 和 T 细胞受体 (TCR) 测序样本 (scRNA TCRαβ-seq) (n = 7)。 CML 中自然杀伤 (NK) 细胞数量较多且表型活跃，将其与健康癌症和其他癌症区分开来。 CML 中的大多数 NK 细胞属于活跃的 CD56dim 簇，高表达 GZMA/B、PRF1、CCL3/4 和 IFNG，并通过抑制性 LGALS9-TIM3 和 PVR-TIGIT 相互作用与白血病细胞相互作用。因此，当共培养时，在 CML 靶细胞中观察到 LGALS9 的上调，在 NK 细胞中观察到 TIM3 的上调。此外，我们创建了一个分类器来识别针对白血病相关抗原 PR1 的 TCR，并定量 90 个 CML 和 786 个健康 TCRβ 测序样本中的抗 PR1 T 细胞。抗 PR1 T 细胞在 CML 中更为普遍，在骨髓样本中富集，并在成熟的细胞毒性 CD8  TEMRA 簇中富集，尤其是在维持 TFR 的患者中。我们的结果强调了 NK 细胞和抗 PR1 T 细胞在 CML 抗白血病免疫反应中的作用。© 2023。作者。

Immunological control of residual leukemia cells is thought to occur in patients with chronic myeloid leukemia (CML) that maintain treatment-free remission (TFR) following tyrosine kinase inhibitor (TKI) discontinuation. To study this, we analyzed 55 single-cell RNA and T cell receptor (TCR) sequenced samples (scRNA+TCRαβ-seq) from patients with CML (n = 13, N = 25), other cancers (n = 28), and healthy (n = 7). The high number and active phenotype of natural killer (NK) cells in CML separated them from healthy and other cancers. Most NK cells in CML belonged to the active CD56dim cluster with high expression of GZMA/B, PRF1, CCL3/4, and IFNG, with interactions with leukemic cells via inhibitory LGALS9-TIM3 and PVR-TIGIT interactions. Accordingly, upregulation of LGALS9 was observed in CML target cells and TIM3 in NK cells when co-cultured together. Additionally, we created a classifier to identify TCRs targeting leukemia-associated antigen PR1 and quantified anti-PR1 T cells in 90 CML and 786 healthy TCRβ-sequenced samples. Anti-PR1 T cells were more prevalent in CML, enriched in bone marrow samples, and enriched in the mature, cytotoxic CD8 + TEMRA cluster, especially in a patient maintaining TFR. Our results highlight the role of NK cells and anti-PR1 T cells in anti-leukemic immune responses in CML.© 2023. The Author(s).