Although immunotherapy has revolutionized cancer treatment, many patients still experience limited benefit, highlighting the urgent need for improved biomarkers1. Although immunotherapy is founded on unleashing T cells2, most existing biomarkers remain tumour-centric and mainly overlook host immune competence. The thymus is a key immune organ that is crucial for T cell maturation, and we hypothesized that thymic functionality is associated with immunotherapy outcomes3. Here we show that thymic health, a radiographic measure of thymic functionality, is strongly associated with immunotherapy outcomes across several cancer types. Using a deep-learning framework applied to routine computed tomography images, we quantified thymic health in a pan-cancer cohort of 3,476 patients receiving immune checkpoint inhibitors. In patients with non-small cell lung cancer, higher thymic health was associated with reduced risks of progression and all-cause mortality. These associations remained significant across clinically relevant levels of programmed death ligand 1 (PD-L1) and tumour mutation burden. In the prospective TRACERx lung cancer study, thymic health was positively associated with T cell receptor diversity and T cell receptor excision circles, and correlated with immune-system signalling pathways, supporting radiographic thymic health as a proxy for thymic activity and adaptive immune competence. Analysis across patients with melanoma, breast cancer or renal cancer demonstrated pan-cancer relevance. Together, these findings identify thymic health as a previously unrecognized, tumour-agnostic determinant of immunotherapy efficacy, with potential implications for patient stratification, treatment timing and the development of immune-rejuvenating strategies in precision immuno-oncology.
尽管免疫疗法已革新癌症治疗，但许多患者的获益仍然有限，凸显出改进生物标志物的迫切需求1。虽然免疫疗法基于T细胞的激活2，但现有大多数生物标志物仍以肿瘤为中心，主要忽略了宿主的免疫能力。胸腺是关键的免疫器官，对T细胞成熟至关重要，我们推测胸腺功能与免疫疗法结局相关3。本研究表明，胸腺健康（一种通过影像学测量的胸腺功能指标）与多种癌症类型的免疫疗法结局密切相关。利用应用于常规计算机断层扫描图像的深度学习框架，我们量化了接受免疫检查点抑制剂治疗的3,476例泛癌队列患者的胸腺健康。在非小细胞肺癌患者中，较高的胸腺健康与进展风险和全因死亡风险降低相关。在临床相关的程序性死亡配体1（PD-L1）表达水平和肿瘤突变负荷水平下，这些关联仍保持显著。在前瞻性TRACERx肺癌研究中，胸腺健康与T细胞受体多样性及T细胞受体删除环呈正相关，并与免疫系统信号通路相关，支持将影像学胸腺健康作为胸腺活性和适应性免疫能力的替代指标。对黑色素瘤、乳腺癌或肾癌患者的分析显示了其泛癌种相关性。综上，这些发现将胸腺健康确认为一种此前未知的、不依赖于肿瘤类型的免疫疗法疗效决定因素，对精准免疫肿瘤学中的患者分层、治疗时机把握以及免疫再生策略开发具有潜在意义。
Thymic health and immunotherapy outcomes in patients with cancer
肿瘤(癌症)患者之家