成熟 T 细胞淋巴瘤是一种异质性肿瘤，具有侵袭性且对治疗有抵抗力。许多这些癌症保留了其起源细胞的免疫学特性。它们表达通常由未转化 T 细胞中的 TCR 信号传导诱导的细胞因子、细胞毒性酶和细胞表面配体。直到最近，它们的分子机制尚不清楚。最近，高维研究改变了我们对其细胞和遗传特征的理解。 TCR 信号通路中的体细胞突变通过破坏自身抑制结构域、增加与配体的亲和力和/或诱导 TCR 独立信号传导来驱动淋巴瘤发生。总的来说，大多数突变都会增强 TCR 下游的信号通路。新数据表明，这些突变不仅促进增殖，还决定淋巴瘤免疫表型。例如，RHOA 突变足以诱导疾病相关的 CD4 T 滤泡辅助细胞表型。在这篇综述中，我们描述了 TCR 信号通路中的突变如何阐明淋巴瘤病理生理学，同时也提供了对更广泛的 T 细胞生物学的见解。版权所有 © 2023 美国免疫学家协会，Inc.

Mature T cell lymphomas are heterogeneous neoplasms that are aggressive and resistant to treatment. Many of these cancers retain immunological properties of their cell of origin. They express cytokines, cytotoxic enzymes, and cell surface ligands normally induced by TCR signaling in untransformed T cells. Until recently, their molecular mechanisms were unclear. Recently, high-dimensional studies have transformed our understanding of their cellular and genetic characteristics. Somatic mutations in the TCR signaling pathway drive lymphomagenesis by disrupting autoinhibitory domains, increasing affinity to ligands, and/or inducing TCR-independent signaling. Collectively, most of these mutations augment signaling pathways downstream of the TCR. Emerging data suggest that these mutations not only drive proliferation but also determine lymphoma immunophenotypes. For example, RHOA mutations are sufficient to induce disease-relevant CD4+ T follicular helper cell phenotypes. In this review, we describe how mutations in the TCR signaling pathway elucidate lymphoma pathophysiology but also provide insights into broader T cell biology.Copyright © 2023 by The American Association of Immunologists, Inc.