TCF1 and its homologue LEF1 are historically known as effector transcription factors downstream of the WNT signalling pathway and are essential for early T cell development. Recent advances bring TCF1 into the spotlight for its versatile, context-dependent functions in regulating mature T cell responses. In the cytotoxic T cell lineages, TCF1 is required for the self-renewal of stem-like CD8⁺ T cells generated in response to viral or tumour antigens, and for preserving heightened responses to checkpoint blockade immunotherapy. In the helper T cell lineages, TCF1 is indispensable for the differentiation of T follicular helper and T follicular regulatory cells, and crucially regulates immunosuppressive functions of regulatory T cells. Mechanistic investigations have also identified TCF1 as the first transcription factor that directly modifies histone acetylation, with the capacity to bridge transcriptional and epigenetic regulation. TCF1 also has the potential to become an important clinical biomarker for assessing the prognosis of tumour immunotherapy and the success of viral control in treating HIV and hepatitis C virus infection. Here, we summarize the key findings on TCF1 across the fields of T cell immunity and reflect on the possibility of exploring TCF1 and its downstream transcriptional programmes as therapeutic targets for improving antiviral and antitumour immunity.

TCF1 及其同系物 LEF1 在历史上被称为 WNT 信号通路下游的效应转录因子，对早期 T 细胞发育至关重要。最近的进展使 TCF1 因其在调节成熟 T 细胞反应方面的多功能、依赖于上下文的功能而受到关注。^{在细胞毒性 T 细胞谱系中，干细胞样 CD8 +}的自我更新需要 TCF1T 细胞响应病毒或肿瘤抗原而产生，并用于保持对检查点阻断免疫疗法的增强反应。在辅助性 T 细胞谱系中，TCF1 对于 T 滤泡辅助细胞和 T 滤泡调节细胞的分化是必不可少的，并且至关重要地调节调节性 T 细胞的免疫抑制功能。机制研究还发现 TCF1 是第一个直接修饰组蛋白乙酰化的转录因子，具有连接转录和表观遗传调控的能力。TCF1 也有可能成为评估肿瘤免疫治疗预后以及病毒控制在治疗 HIV 和丙型肝炎病毒感染中是否成功的重要临床生物标志物。这里，