RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Donor selection based on NK alloreactivity for patients with hematological malignancies.
Donor selection based on NK alloreactivity for patients with hematological malignancies.
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自然杀伤(NK)细胞是抵御感染和肿瘤的重要防御细胞,其功能由抑制性受体和激活性受体之间的平衡调节。在所有NK抑制性受体中,杀伤细胞免疫球蛋白样受体(KIR)和CD94/NKG2A可识别人白细胞抗原(HLA)I类分子,使NK细胞获得“许可”,既避免自身反应,又保持充分功能。获得许可的NK细胞可靶向“自我”抗原异常表达、下调或缺失的恶性细胞。NK细胞攻击恶性细胞是移植物抗白血病(GVL)效应的机制之一。大量研究证明,NK细胞可通过GVL效应降低复发相关死亡率,从而改善造血干细胞移植(HCT)生存。治疗策略包括过继异体反应性NK细胞转移、CAR-NK细胞,以及抗NKG2A和KIR2DL1–3抗体,已用于治疗HCT背景下的血液系统恶性肿瘤。本文综述NK细胞功能、受体和配体,以及HCT治疗血液系统恶性肿瘤患者时常用的异体反应性NK供者选择算法。本文旨在阐释有争议的研究结果,并提供更好的理解和资源,以指导HCT中的异体反应性供者NK细胞选择。
Natural killer (NK) cells are an important defender against infections and tumors. Their function is regulated by the balance of inhibitory and activating receptors. Among all inhibitory NK receptors: killer immunoglobulin-like receptors (KIR) and CD94/NKG2A recognize human leukocyte antigen (HLA) Class I molecules, allowing NK cells to be 'licensed' to avoid autoreactivity, but be fully functional at the same time. Licensed NK cells can target malignant cells with altered or downregulated/missing 'self' antigens. NK cell attacking malignant cells is one of the mechanisms of graft-versus-leukemia (GVL) effect.
Numerous studies have demonstrated that NK cells improve hematopoietic stem cell transplantation (HCT) survival by reducing relapse mortality through GVL effect. Therapeutic strategies, such as adoptive alloreactive NK cell transfer, CAR-NK cells, antibodies against NKG2A and KIR2DL1-3, have been utilized to treat hematological malignancies in HCT.
In this review, NK cell functions, NK cell receptors and ligands, as well as common alloreactive NK donor selection algorithms for patients with hematological malignancies in the setting of HCT are discussed. The goal of this review is to provide insights on the controversial results and provide better understanding and resources on how to perform alloreactive donor NK cell selection in HCT.
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