Peripheral T-cell lymphomas (PTCLs) encompass a heterogeneous group of postthymic T-cell lymphomas with >30 distinct subtypes associated with varied clinicopathological features. Unfortunately, the overall survival of the major PTCL subtypes is dismal and has not improved for decades; thus, there is an urgent unmet clinical need to improve diagnosis, therapies, and clinical outcomes. The diagnosis is often challenging, requiring a combinatorial evaluation of clinical, morphologic, and immunophenotypic features. PTCL pathobiology is difficult to investigate due to enormous intertumor and intratumor heterogeneity, limited tissue availability, and the paucity of authentic T-cell lymphoma cell lines or genetically faithful animal models. The application of transcriptomic profiling and genomic sequencing has markedly accelerated the discovery of new biomarkers, molecular signatures, and genetic lesions, and some of the discoveries have been included in the revised World Health Organization or International Consensus Classification. Genome-wide investigations have revealed the mutational landscape and transcriptomic profiles of PTCL entities, defined the cell of origin as a major determinant of T-cell lymphoma biology, and allowed for the refinement of biologically and clinically meaningful entities for precision therapy. In this review, we prioritize the discussion on common nodal PTCL subtypes together with 2 virus-associated T-cell and natural killer cell lymphomas. We succinctly review normal T-cell development, differentiation, and T-cell receptor signaling as they relate to PTCL pathogenesis and biology. This review will facilitate a better biological understanding of the different PTCL entities and their stratification for additional studies and target-directed clinical trials.

中文翻译：

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对 T 细胞淋巴瘤生物学的新见解


外周 T 细胞淋巴瘤 （PTCLs） 包括一组异质性的胸腺后 T 细胞淋巴瘤，具有与不同临床病理特征相关的 >30 不同亚型。不幸的是，主要 PTCL 亚型的总体生存率很低，几十年来没有改善;因此，存在迫切的未满足的临床需求，以改善诊断、治疗和临床结果。诊断通常具有挑战性，需要对临床、形态学和免疫表型特征进行组合评估。由于肿瘤间和肿瘤内异质性巨大、组织可用性有限以及缺乏真正的 T 细胞淋巴瘤细胞系或遗传忠实的动物模型，因此很难研究 PTCL 病理生物学。转录组学分析和基因组测序的应用显著加速了新生物标志物、分子特征和遗传病变的发现，其中一些发现已被纳入修订后的世界卫生组织或国际共识分类。全基因组研究揭示了 PTCL 实体的突变景观和转录组学特征，将起源细胞定义为 T 细胞淋巴瘤生物学的主要决定因素，并允许改进具有生物学和临床意义的实体以进行精准治疗。在本综述中，我们优先讨论常见的淋巴结 PTCL 亚型以及 2 种病毒相关 T 细胞和自然杀伤细胞淋巴瘤。我们简要回顾了正常的 T 细胞发育、分化和 T 细胞受体信号传导，因为它们与 PTCL 发病机制和生物学有关。 本综述将有助于更好地了解不同的 PTCL 实体及其分层，以便进行更多研究和靶向临床试验。