累积的临床前和临床证据表明，放射治疗可能增强免疫治疗对非小细胞肺癌的全身抗肿瘤反应，但联合治疗的最佳时机仍不清楚。肿瘤浸润CD8+ T细胞的总浸润和疲劳亚群可能是潜在的生物标志，表明对免疫检查点抑制剂（ICI）的反应，其变化在放疗期间之前未经表征，而在临床实践中无法通过重复活检进行动态监测。基于肿瘤携带的小鼠模型，我们研究了消融放射后CD8+ T细胞总浸润和耗竭亚群的动态变化。在了解伴随T细胞耗竭的不同代谢特性的基础上，我们开发了一种PET放射组学方法来识别和可视化T细胞耗竭状态。消融放射后3至14天，CD8+ T细胞浸润增加，而在这一浸润期间的后期，毕生耗竭人口显着占主导地位，表明消融后3-7天可能是适当的ICI治疗窗口。建立了PET放射组学方法，以区分T细胞耗竭状态，在ICI和放射设置中均适用。我们还将PET图像上更多的异质纹理与进展的T细胞耗竭联系起来。我们提出了一种非侵入性影像预测程序，可以准确评估与ICI治疗和放疗相关的异质性T细胞耗竭状态，并可能成为及时估计肿瘤微环境的免疫响应性和联合治疗的最佳时机的有前途的解决方案。©2023 The Author(s)。

Cumulative preclinical and clinical evidences showed radiotherapy might augment systemic antitumoral responses to immunotherapy for metastatic non-small cell lung cancer, but the optimal timing of combination is still unclear. The overall infiltration and exhausted subpopulations of tumor-infiltrating CD8+ T cells might be a potential biomarker indicating the response to immune checkpoint inhibitors (ICI), the alteration of which is previously uncharacterized during peri-irradiation period, while dynamic monitoring is unavailable via repeated biopsies in clinical practice.Basing on tumor-bearing mice model, we investigated the dynamics of overall infiltration and exhausted subpopulations of CD8+ T cells after ablative irradiation. With the understanding of distinct metabolic characteristics accompanied with T cell exhaustion, we developed a PET radiomics approach to identify and visualize T cell exhaustion status.CD8+ T cell infiltration increased from 3 to 14 days after ablative irradiation while terminally exhausted populations significantly predominated CD8+ T cells during late course of this infiltrating period, indicating that 3-7 days post-irradiation might be a potential appropriate window for delivering ICI treatment. A PET radiomics approach was established to differentiate T cell exhaustion status, which fitted well in both ICI and irradiation settings. We also visualized the underlying association of more heterogeneous texture on PET images with progressed T cell exhaustion.We proposed a non-invasive imaging predictor which accurately assessed heterogeneous T cell exhaustion status relevant to ICI treatment and irradiation, and might serve as a promising solution to timely estimate immune-responsiveness of tumor microenvironment and the optimal timing of combined therapy.© 2023. The Author(s).