Abstract：
Primary central nervous system lymphoma (PCNSL) is a rare and highly aggressive lymphoma entirely localized in the central nervous system or vitreoretinal space. PCNSL generally initially responds to methotrexate-containing chemotherapy regimens, but progressive or relapsing disease is common, and the prognosis is poor for relapsed or refractory (R/R) patients. PCNSL is often characterized by activation of nuclear factor kappa B (NF-κB) due to mutations in the B-cell receptor (BCR) or toll-like receptor (TLR) pathways, as well as immune evasion. Targeted treatments that inhibit key PCNSL mechanisms and pathways are being evaluated; inhibition of Bruton\'s tyrosine kinase (BTK) downstream of BCR activation has demonstrated promising results in treating R/R disease. This review will summarize the evidence and potential for targeted therapeutic agents to improve treatment outcomes in PCNSL. This includes immunotherapeutic and immunomodulatory approaches and inhibitors of the key pathways driving PCNSL, such as aberrant BCR and TLR signaling.
摘要：
原发性中枢神经系统淋巴瘤（PCNSL）是一种罕见且高度侵袭性的淋巴瘤，完全位于中枢神经系统或玻璃体视网膜间隙。PCNSL通常最初对含甲氨蝶呤的化疗方案有反应，但是进展性或复发性疾病很常见，复发或难治性（R/R）患者的预后较差。PCNSL的特征通常是由于B细胞受体（BCR）或Toll样受体（TLR）途径中的突变而激活核因子κB（NF-κB）。以及免疫逃避。正在评估抑制关键PCNSL机制和途径的靶向治疗；抑制BCR激活下游的Bruton酪氨酸激酶（BTK）已证明在治疗R/R疾病方面取得了有希望的结果。这篇综述将总结靶向治疗药物改善PCNSL治疗结果的证据和潜力。这包括免疫治疗和免疫调节方法以及驱动PCNSL的关键途径的抑制剂，如异常的BCR和TLR信号。
