Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most effective treatment for selected patients with acute myeloid leukemia (AML) and relies on a "graft-versus-leukemia" effect (GVL) where donor T lymphocytes mediate control of malignant cell growth. However, relapse remains the major cause of death after allo-HSCT. In various malignancies, several immunoregulatory mechanisms have been shown to restrain antitumor immunity, including ligand-mediated engagement of inhibitory receptors (IRs) on effector cells, and induction of immunosuppressive cell subsets, such as regulatory T cells (Tregs) or myeloid-derived suppressor cells (MDSCs). Relapse after HSCT remains a major therapeutic challenge, but immunoregulatory mechanisms involved in restraining the GVL effect must be better deciphered in humans. We used mass cytometry to comprehensively characterize circulating leukocytes in 2 cohorts of patients after allo-HSCT. We first longitudinally assessed various immunoregulatory parameters highlighting specific trends, such as opposite dynamics between MDSCs and Tregs. More generally, the immune landscape was stable from months 3 to 6, whereas many variations occurred from months 6 to 12 after HSCT. Comparison with healthy individuals revealed that profound alterations in the immune equilibrium persisted 1 year after HSCT. Importantly, we found that high levels of TIGIT and CD161 expression on CD4 T cells at month 3 after HSCT were distinct features significantly associated with subsequent AML relapse in a second cross-sectional cohort. Altogether, these data provide global insights into the reconstitution of the immunoregulatory landscape after HSCT and highlight non-canonical IRs associated with relapse, which could open the path to new prognostic tools or therapeutic targets to restore subverted anti-AML immunity.

中文翻译：

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allo-HSCT 后的免疫景观：表达 TIGIT 和 CD161 的 CD4 T 细胞与随后的白血病复发有关。

同种异体造血干细胞移植 (allo-HSCT) 是选定的急性髓性白血病 (AML) 患者最有效的治疗方法，它依赖于供体 T 淋巴细胞介导恶性细胞生长控制的“移植物抗白血病”效应 (GVL) . 然而，复发仍然是 allo-HSCT 后死亡的主要原因。在各种恶性肿瘤中，一些免疫调节机制已被证明可以抑制抗肿瘤免疫，包括配体介导的抑制性受体 (IR) 对效应细胞的参与，以及免疫抑制细胞亚群的诱导，例如调节性 T 细胞 (Treg) 或骨髓来源的抑制因子细胞（MDSC）。HSCT 后的复发仍然是一个主要的治疗挑战，但必须在人类中更好地破译参与抑制 GVL 效应的免疫调节机制。我们使用质谱流式细胞术全面表征 2 组患者在异基因造血干细胞移植后的循环白细胞。我们首先纵向评估了突出特定趋势的各种免疫调节参数，例如 MDSC 和 Treg 之间的相反动力学。更一般地说，免疫环境在 3 到 6 个月期间是稳定的，而在 HSCT 后的 6 到 12 个月期间发生了许多变化。与健康个体的比较表明，在 HSCT 后 1 年，免疫平衡的深刻改变仍然存在。重要的是，我们发现在第二个横断面队列中，HSCT 后第 3 个月 CD4 T 细胞上高水平的 TIGIT 和 CD161 表达是与随后的 AML 复发显着相关的明显特征。共，