在T细胞中发挥双刃剑作用的分子:对过继T细胞治疗的启示。

Marziyeh Samiee, Saeedeh Salehi, Leila Mohamed Khosroshahi, Tahereh Soltantoyeh
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引用次数: 0

摘要

传统上,免疫检查点被视为抑制分子,下调免疫细胞活性,作为防止过度免疫反应的保障。然而,在慢性感染和癌症中,这些检查点充当屏障,可以抑制有效的免疫反应,从而减少病理后果。多年来,研究人员通过基于抗体的疗法探索免疫检查点阻断,并寻求在过继性T细胞疗法中删除这些分子以增强T细胞功能和增殖。然而,新的研究表明,免疫检查点删除可能并不总是有利的;这些分子似乎在支持T细胞代谢、细胞毒性、增殖和持久性等功能方面发挥着复杂的作用。其中一些可能在T细胞分化为记忆细胞等亚群的过程中起作用。本文深入研究了免疫检查点分子,如PD-1、TIM-2、A2aR、2B4和EP2,强调了它们在免疫调节中的微妙作用和对免疫治疗的影响。我们建议应将这些分子视为一把双刃剑,并考虑到它们鲜为人知的作用和其他相互作用因素,更加谨慎地加以调节。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Molecules with Double-Edged Sword Roles in T Cell: An Implication for Adoptive T Cell Therapy.

Immune checkpoints have traditionally been viewed as inhibitory molecules that downregulate immune cell activity, acting as a safeguard against excessive immune responses. In chronic infections and cancer, however, these checkpoints serve as barriers that can inhibit effective immune responses, thereby reducing pathological consequences. Over the years, researchers have explored immune checkpoint blockade through antibody-based therapies and have sought to delete these molecules in adoptive T cell therapy to enhance T cell function and proliferation. However, emerging research suggests that immune checkpoint deletion may not always be advantageous; these molecules appear to play complex roles in supporting T cell functions like metabolism, cytotoxicity, proliferation and persistence. Some of them might have roles in T cell differentiation into subsets like memory cells. This article delves into the evolving understanding of immune checkpoint molecules, such as PD-1, TIM-2, A2aR, 2B4 and EP2, highlighting their nuanced roles in immune regulation and implications for immunotherapy. We proposed that these molecules should be viewed as a double-edged sword and regulated with greater caution, taking into account their lesser-known roles and other interacting factors.

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