Department of Experimental Immunotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
Department of Biotechnology, Sardar Bahadur Khan Womens' University, Balochistan, Pakistan.
Front Immunol. 2023 May 15;14:1155468. doi: 10.3389/fimmu.2023.1155468. eCollection 2023.
Recent discoveries shed light on molecular mechanisms responsible for classical Hodgkin lymphoma (HL) development and progression, along with features of Hodgkin - Reed and Sternberg cells (HRS). Here, we summarize current knowledge on characteristic molecular alterations in HL, as well as existing targeted therapies and potential novel treatments for this disease. We discuss the importance of cluster of differentiation molecule 30 (CD30) and the programmed cell death-1 protein (PD-1) and ligands (PD-L1/2), and other molecules involved in immune modulation in HL. We highlight emerging evidence indicating that the altered function of SWI/SNF-type chromatin remodeling complexes, PRC2, and other epigenetic modifiers, contribute to variations in chromatin status, which are typical for HL. We postulate that despite of the existence of plentiful molecular data, the understanding of HL development remains incomplete. We therefore propose research directions involving analysis of reverse signaling in the PD-1/PD-L1 mechanism, chromatin remodeling, and epigenetics-related alterations, in order to identify HL features at the molecular level. Such attempts may lead to the identification of new molecular targets, and thus will likely substantially contribute to the future development of more effective targeted therapies.
最近的发现揭示了导致经典霍奇金淋巴瘤(HL)发展和进展的分子机制,以及霍奇金-里德和斯特恩伯格细胞(HRS)的特征。在这里,我们总结了 HL 中特征性分子改变的现有知识,以及针对这种疾病的现有靶向治疗和潜在的新治疗方法。我们讨论了分化群分子 30(CD30)和程序性细胞死亡蛋白 1 配体(PD-L1/2)以及其他参与 HL 免疫调节的分子的重要性。我们强调了新出现的证据,表明 SWI/SNF 型染色质重塑复合物、PRC2 和其他表观遗传修饰物的功能改变导致了 HL 典型的染色质状态的变化。我们假设,尽管存在大量的分子数据,但对 HL 发展的理解仍然不完整。因此,我们提出了涉及 PD-1/PD-L1 机制、染色质重塑和表观遗传学相关改变的反向信号分析的研究方向,以便在分子水平上识别 HL 的特征。这些尝试可能会识别出新的分子靶点,从而为未来更有效的靶向治疗的发展做出重大贡献。
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