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Implication of TET2 in CAR-T cell activity and target’s response to CAR-T cell therapy. Lessons learned from T-cells
Critical Reviews in Immunology ( IF 0.8 ) Pub Date : 2020-12-01 , DOI: 10.1615/critrevimmunol.2020036946
Sergiu Pasca 1 , Ancuta Jurj 2 , Catalin Constantinescu 3 , Mihnea Zdrenghea 4 , Ciprian Tomuleasa 5
Affiliation  

Chimeric antigen receptor T (CAR-T) cell therapy is a recent therapeutic acquisition in the field of oncology, the first one approved being represented by tisagenlecleucel, followed short after by the approval of axicabtagene ciloleucel. Because this product is derived from T-cells, there are several lessons that can be learned from T-cell biology to better understand CAR-T cells. Thus, in this review, we will discuss the effects that TET2 can have in T-cells, macrophages interacting with T-cells or in non-immune cells. In T-cells, TET2 mutations have been frequently shown to be associated with FOXP3 expression reduction and instability, which leads to the reduction in T regulatory (Treg) cells and increase in T-helper (Th)1 and Th17 cells. This alteration in T-cell polarization balance leads both to an enhanced anti-tumor activity and an increased probability of developing autoimmune diseases. In the case of macrophages, TET2 has a similar role, as it’s activity reduction is associated with an M1 signature, while it’s overexpression is associated with an M2 signature. In non-immune cells, the role of TET2 is opposite to it’s role in immune cells. Specifically, the reduction in TET2 activity is associated with a decreased immune response both in the case of malignancies and in the case of autoimmune diseases. Thus, in the current review we have discussed the role that TET2 has regarding T-cell activity and considering the role it has in non-immune cells in relation to T-cells.

中文翻译:

TET2 对 CAR-T 细胞活性和靶点对 CAR-T 细胞治疗反应的影响。从 T 细胞中吸取的教训

嵌合抗原受体 T (CAR-T) 细胞疗法是肿瘤学领域最近的一项治疗收购,第一个获得批准的代表是 tisagenlecleucel,紧随其后的是 axicabtagene ciloleucel 的批准。由于该产品来源于 T 细胞,因此可以从 T 细胞生物学中吸取一些经验教训,以更好地了解 CAR-T 细胞。因此,在这篇综述中,我们将讨论 TET2 对 T 细胞、与 T 细胞相互作用的巨噬细胞或在非免疫细胞中的影响。在 T 细胞中,TET2 突变经常被证明与 FOXP3 表达减少和不稳定有关,这导致 T 调节 (Treg) 细胞减少和 T 辅助 (Th)1 和 Th17 细胞增加。这种 T 细胞极化平衡的改变导致抗肿瘤活性增强和发生自身免疫性疾病的可能性增加。在巨噬细胞的情况下,TET2 具有类似的作用,因为它的活性降低与 M1 特征相关,而它的过度表达与 M2 特征相关。在非免疫细胞中,TET2 的作用与其在免疫细胞中的作用相反。具体而言,在恶性肿瘤和自身免疫性疾病的情况下,TET2 活性的降低与免疫反应的降低有关。因此,在当前的审查中,我们讨论了 TET2 在 T 细胞活性方面的作用,并考虑了它在非免疫细胞中与 T 细胞相关的作用。因为它的活性降低与 M1 特征相关,而它的过度表达与 M2 特征相关。在非免疫细胞中,TET2 的作用与其在免疫细胞中的作用相反。具体而言,在恶性肿瘤和自身免疫性疾病的情况下,TET2 活性的降低与免疫反应的降低有关。因此,在当前的审查中,我们讨论了 TET2 在 T 细胞活性方面的作用,并考虑了它在非免疫细胞中与 T 细胞相关的作用。因为它的活性降低与 M1 特征相关,而它的过度表达与 M2 特征相关。在非免疫细胞中,TET2 的作用与其在免疫细胞中的作用相反。具体而言,在恶性肿瘤和自身免疫性疾病的情况下,TET2 活性的降低与免疫反应的降低有关。因此,在当前的审查中,我们讨论了 TET2 在 T 细胞活性方面的作用,并考虑了它在非免疫细胞中与 T 细胞相关的作用。在恶性肿瘤和自身免疫性疾病的情况下,TET2 活性的降低与免疫反应的降低有关。因此,在当前的审查中,我们讨论了 TET2 在 T 细胞活性方面的作用,并考虑了它在非免疫细胞中与 T 细胞相关的作用。在恶性肿瘤和自身免疫性疾病的情况下,TET2 活性的降低与免疫反应的降低有关。因此,在当前的审查中,我们讨论了 TET2 在 T 细胞活性方面的作用,并考虑了它在非免疫细胞中与 T 细胞相关的作用。
更新日期:2020-12-16
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