Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Front Immunol. 2020 Aug 4;11:1769. doi: 10.3389/fimmu.2020.01769. eCollection 2020.
Regulatory T cells (Tregs), which have long been recognized as essential regulators of both inflammation and autoimmunity, also impede effective antitumor immune response due to their immunosuppressive properties. Combined radiotherapy and immunotherapeutic interventions focusing on the removal of Tregs have recently garnered interest as a promising strategy to reverse immunosuppression. Meanwhile, Tregs are emerging as a key player in the pathogenesis of radiation-induced lung injury (RILI), a frequent and potentially life-threatening complication of thoracic radiotherapy. Recognition of the critical role of Tregs in RILI raises the important question of whether radiotherapy combined with Treg-targeting immunotherapy offers any beneficial effects in the protection of normal lung tissue. This present review focuses on the contributions of Tregs to RILI, with particular emphasis on the suspected differential role of Tregs in the pneumonitic phase and fibrotic phase of RILI. We also introduce recent progress on the potential mechanisms by which Tregs modulate RILI and the crosstalk among Tregs, other infiltrating T cells, fibrocytes, and resident epithelial cells driving disease pathogenesis. Finally, we discuss whether Tregs also hold promise as a potential target for immunotherapeutic interventions for RILI.
调节性 T 细胞（Tregs）长期以来一直被认为是炎症和自身免疫的重要调节者，但其免疫抑制特性也会阻碍有效的抗肿瘤免疫反应。由于其免疫抑制特性，联合放疗和免疫治疗干预措施，旨在消除 Tregs，最近引起了人们的兴趣，成为逆转免疫抑制的一种有前途的策略。同时，Tregs 也成为放射性肺损伤（RILI）发病机制中的关键因素，RILI 是胸部放疗的常见且潜在危及生命的并发症。Tregs 在 RILI 中的关键作用得到了认可，这就提出了一个重要问题，即放疗联合 Treg 靶向免疫疗法是否对保护正常肺组织有任何有益效果。本综述重点关注 Tregs 对 RILI 的贡献，特别强调 Tregs 在 RILI 的气肿期和纤维化期的疑似差异作用。我们还介绍了 Tregs 调节 RILI 的潜在机制以及 Tregs、其他浸润性 T 细胞、纤维母细胞和驻留上皮细胞之间的串扰，这些都推动了疾病的发病机制。最后，我们讨论了 Tregs 是否也有希望成为 RILI 免疫治疗干预的潜在靶点。
