肿瘤细胞治疗研究
英文原题：From molecular pathogenesis to novel Therapeutic approaches - a review of recent advances in the treatment of peripheral T cell Lymphomas.
外周T细胞淋巴瘤（PTCLs）包括约30种不同的亚型，合计约占所有非霍奇金淋巴瘤的10-20%，其地理分布以东亚和南美更为多见。
外周T细胞淋巴瘤（PTCLs）包括约30种不同的亚型，合计约占所有非霍奇金淋巴瘤的10-20%，其地理分布以东亚和南美洲更为多见。它们在肿瘤生物学、微环境组成和化疗敏感性方面存在显著差异。标准一线治疗仍为以蒽环类药物为基础的方案，如CHOP（环磷酰胺、多柔比星、长春新碱和泼尼松龙）。除ALK+间变性大细胞淋巴瘤（ALCL）外，此类治疗在大多数组织学亚型中通常临床结局不佳。PTCL的肿瘤发生由遗传和表观遗传畸变、T细胞受体（TCR）信号失调以及微环境重塑的共同作用驱动。这些因素共同破坏细胞存活与凋亡之间的平衡，导致恶性转化。分子特征研究的进展已开始揭示亚型特异性致癌靶点，从而使得靶向治疗的合理开发成为可能。近期的一项重大突破是里程碑式的ECHELON-2试验，该试验促成了brentuximab vedotin（BV）——一种抗CD30抗体-药物偶联物——的获批，其与CHP（环磷酰胺、多柔比星和泼尼松龙）联合已成为CD30阳性PTCL的标准治疗。除brentuximab外，针对PTCL淋巴瘤发生各个方面的新型治疗药物正在积极研究中，其中一些已进入常规临床实践。表观遗传修饰剂包括HDAC抑制剂、去甲基化药物和EZH2抑制剂，利用T滤泡辅助细胞来源淋巴瘤所特有的表观遗传失调。此外，靶向JAK-STAT、PI3K和ALK通路的小分子抑制剂，以及单克隆抗体、双特异性抗体、检查点抑制剂和CAR-T细胞疗法等免疫治疗策略，也处于不同的临床开发阶段。一个未满足的临床需求领域是老年患者中PTCL患病率不断增加，其中治疗毒性是一个主要考虑因素，而此类个体化治疗可能带来最大获益。
Peripheral T-cell lymphomas (PTCLs) comprise approximately 30 distinct subtypes, collectively accounting for around 10-20% of all non-Hodgkin lymphomas, with a geographic distribution that is more predominant in East Asia and South America. They differ significantly in tumor biology, microenvironmental composition, and chemosensitivity. Standard frontline therapy remains anthracycline-based regimens such as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone). With the exception of ALK+ anaplastic large cell lymphoma (ALCL), such treatments typically yield poor clinical outcomes in most histological subtypes. Oncogenesis in PTCL is driven by a convergence of genetic and epigenetic aberrations, T-cell receptor (TCR) signaling dysregulation and microenvironmental remodeling. Together, they disrupt the balance between cell survival and apoptosis, leading to malignant transformation. Advances in molecular characterization have started to shed light on subtype-specific oncogenic targets, thus allowing for rational development of targeted therapies. A major recent breakthrough was the landmark ECHELON-2 trial, which has led to the approval of brentuximab vedotin (BV), an anti-CD30 antibody-drug conjugate, which in combination with CHP (cyclophosphamide, doxorubicin and prednisolone) has become the standard of care for CD30-positive PTCLs. Beyond brentuximab, novel therapeutic agents targeting various aspects of PTCL lymphomagenesis are under active investigation, with some already entering routine clinical practice. Epigenetic modifiers including HDAC inhibitors, hypomethylating agents, and EZH2 inhibitors exploit the epigenetic dysregulation characteristic of T-follicular helper cell-derived lymphomas. In addition, small molecule inhibitors targeting JAK-STAT, PI3K, and ALK pathways, as well as immunotherapy strategies such as monoclonal antibodies, bispecific antibodies, checkpoint inhibitors, and CAR-T cell therapy, are also in varying stages of clinical development. An area of unmet clinical need is the increasing prevalence of PTCL in older patients, where treatment toxicity is a major consideration, and where such tailored treatment might yield the greatest benefit.
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