Centro de Investigaciones Oncológicas, Fundación Cáncer (CIO-FUCA), Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
Hematology Department, Fundación para combatir la leucemia (FUNDALEU), Buenos Aires, Argentina.
Front Immunol. 2023 Sep 25;14:1241600. doi: 10.3389/fimmu.2023.1241600. eCollection 2023.
Treatment-free remission (TFR) in patients with chronic myeloid leukemia in chronic phase is considered a safe option if suitable molecular monitoring is available. However, the question arises as to which factors can contribute to the maintenance of TFR, and immunologic surveillance of the remaining leukemic cells is believed to be one of them. Argentina Stop Trial is an open-label, single-arm, multicenter trial assessing TFR after tyrosine kinase inhibitors interruption, that after more than 4 years showed a successful TFR rate of 63%.
In this context, we set up an immunological study by flow cytometry in order to analyze specific NK cell subsets from peripheral blood patient samples both at the time of discontinuation as well as during the subsequent months.
At the time of discontinuation, patients show a mature NK cell phenotype, probably associated to TKI treatment. However, 3 months after discontinuation, significant changes in several NK cell receptors occurred. Patients with a higher proportion of CD56dim NK and PD-1+ NK cells showed better chances of survival. More interestingly, non-relapsing patients also presented a subpopulation of NK cells with features associated with the expansion after cytomegalovirus infection (expression of CD57+NKG2C+), and higher proportion of NKp30 and NKp46 natural cytotoxicity receptors, which resulted in greater degranulation and associated with better survival (p<0.0001).
This NK cell subset could have a protective role in patients who do not relapse, thus further characterization could be useful for patients in sustained deep molecular response.
如果有合适的分子监测手段，慢性期慢性髓性白血病患者达到无治疗缓解（TFR）被认为是一种安全的选择。然而，问题是哪些因素有助于维持 TFR，而对残留白血病细胞的免疫监测被认为是其中之一。阿根廷停药试验是一项开放标签、单臂、多中心试验，评估酪氨酸激酶抑制剂停药后的 TFR，该试验在 4 年多后显示出 63%的成功 TFR 率。
在这种情况下，我们通过流式细胞术建立了一项免疫学研究，以分析患者外周血样本中特定的 NK 细胞亚群，包括在停药时以及随后的几个月。
在停药时，患者表现出成熟的 NK 细胞表型，可能与 TKI 治疗有关。然而，停药后 3 个月，NK 细胞受体发生了显著变化。CD56dim NK 和 PD-1+NK 细胞比例较高的患者有更好的生存机会。更有趣的是，无复发患者还表现出具有巨细胞病毒感染后扩增特征的 NK 细胞亚群（表达 CD57+NKG2C+），以及更高比例的 NKp30 和 NKp46 自然细胞毒性受体，这导致脱颗粒更多，并与更好的生存相关（p<0.0001）。
该 NK 细胞亚群在未复发的患者中可能具有保护作用，因此进一步的特征分析可能对持续深度分子反应的患者有用。
