Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay, Mumbai, Maharashtra 400076, India.
Medical Oncology, Tata memorial Hospital, Mumbai, Maharashtra 400012, India.
Pharmacol Ther. 2022 Aug;236:108109. doi: 10.1016/j.pharmthera.2022.108109. Epub 2022 Jan 7.
T cell lymphomas encompass a diverse group of Non-Hodgkin lymphomas with a wide spectrum of clinical, immunological and pathological manifestations. In the last two decades there has been a progress in our understanding of the cell of origin, genetic abnormalities and their impact on behaviour in T cell lymphomas. Genetic alterations are one of the critical drivers of the pathogenesis of T cell lymphoma. Disease progression has been correlated with multiple genetic abnormalities where malignant clones arise primarily out of the host immune surveillance arsenal. There are many cellular processes involved in disease development, and some of them are T cell signaling, differentiation, epigenetic modifications, and immune regulation. Modulation of these crucial pathways via genetic mutations and chromosomal abnormalities possessing either point or copy number mutations helps tumor cells to develop a niche favourable for their growth via metabolic alterations. Several metabolic pathways especially regulation of redox homeostasis is critical in pathogenesis of lymphoma. Disruption of redox potential and induction of oxidative stress renders malignant cells vulnerable to mitochondrial damage and triggers apoptotic pathways causing cell death. Targeting genetic abnormalities and oxidative stress along with current treatment regime have the potential for improved therapeutics and presents new combination approaches towards selective treatment of T cell lymphomas.
T 细胞淋巴瘤包括一组具有广泛临床、免疫和病理表现的非霍奇金淋巴瘤。在过去的二十年中，我们对 T 细胞淋巴瘤的起源细胞、遗传异常及其对行为的影响有了更深入的了解。遗传改变是 T 细胞淋巴瘤发病机制的关键驱动因素之一。疾病的进展与多种遗传异常相关，其中恶性克隆主要源于宿主的免疫监视机制。有许多细胞过程参与疾病的发展，其中一些是 T 细胞信号转导、分化、表观遗传修饰和免疫调节。通过遗传突变和染色体异常（包括点突变和拷贝数突变）对这些关键途径的调节，有助于肿瘤细胞通过代谢改变来发展有利于其生长的小生境。几种代谢途径，特别是氧化还原平衡的调节，在淋巴瘤的发病机制中至关重要。氧化还原势的破坏和氧化应激的诱导使恶性细胞容易受到线粒体损伤，并触发导致细胞死亡的凋亡途径。针对遗传异常和氧化应激以及当前的治疗方案，具有改善治疗效果的潜力，并为 T 细胞淋巴瘤的选择性治疗提供了新的联合方法。
