化疗引起的周围神经病变（CIPN）是抗肿瘤药物（如紫杉醇）的主要剂量限制性副作用之一，其主要症状为疼痛。目前对于CIPN尚无有效治疗，可能导致癌症患者和幸存者长期发病率增加。神经免疫相互作用发生在CIPN疼痛中，并且已经被证明在CIPN疼痛的发展和进展以及CIPN疼痛的缓解方面都有作用。我们调查了激发型共刺激分子（ICOS）在小鼠中缓解CIPN疼痛的潜在作用。ICOS是一种免疫检查点分子，表达在激活的T细胞表面，促进T细胞的增殖和分化。我们发现，脑脊液内给予ICOS激动剂抗体（ICOSaa）可缓解紫杉醇引起的机械过敏，并促进雌性小鼠机械过敏的解决。ICOSaa的给予可减少之前以紫杉醇处理的小鼠脊髓星形胶质细胞增生和DRG卫星细胞胶质细胞增生。机械上皮敏感度的解决机制是通过增加背根神经节中白细胞介素10（IL-10）的表达来促进的。与这些观察结果一致，阻断IL-10受体（IL-10R）的活动可使ICOSaa治疗对雌性小鼠的机械上皮敏感度无效。 ICOSaa在神经病理性疼痛的范围内也可部分解决剩余神经损伤（SNI）模型的机械过敏。我们的研究支持这样的一个模型，ICOSaa的给予可引起白细胞介素10（IL-10）的表达，以促进雌性小鼠神经病理性疼痛的缓解。ICOSaa的治疗正在临床开发中用于实体瘤，鉴于我们在人类DRG中观察到的T细胞，ICOSaa疗法可以用于联合化疗-CIPN临床试验。© 2023.该作者。

Chemotherapy-induced peripheral neuropathy (CIPN) is a primary dose-limiting side effect caused by antineoplastic agents, such as paclitaxel. A primary symptom of this neuropathy is pain. Currently, there are no effective treatments for CIPN, which can lead to long-term morbidity in cancer patients and survivors. Neuro-immune interactions occur in CIPN pain and have been implicated both in the development and progression of pain in CIPN and the resolution of pain in CIPN. We investigated the potential role of inducible co-stimulatory molecule (ICOS) in the resolution of CIPN pain-like behaviors in mice. ICOS is an immune checkpoint molecule that is expressed on the surface of activated T cells and promotes proliferation and differentiation of T cells. We found that intrathecal administration of ICOS agonist antibody (ICOSaa) alleviates mechanical hypersensitivity caused by paclitaxel and facilitates the resolution of mechanical hypersensitivity in female mice. Administration of ICOSaa reduced astrogliosis in the spinal cord and satellite cell gliosis in the DRG of mice previously treated with paclitaxel. Mechanistically, ICOSaa intrathecal treatment promoted mechanical hypersensitivity resolution by increasing interleukin 10 (IL-10) expression in the dorsal root ganglion. In line with these observations, blocking IL-10 receptor (IL-10R) activity occluded the effects of ICOSaa treatment on mechanical hypersensitivity in female mice. Suggesting a broader activity in neuropathic pain, ICOSaa also partially resolved mechanical hypersensitivity in the spared nerve injury (SNI) model. Our findings support a model wherein ICOSaa administration induces IL-10 expression to facilitate neuropathic pain relief in female mice. ICOSaa treatment is in clinical development for solid tumors and given our observation of T cells in the human DRG, ICOSaa therapy could be developed for combination chemotherapy-CIPN clinical trials.© 2023. The Author(s).