Zeng Weibiao, Wang Jin, Chen Zhike, Yang Jian, Zhu Ao, Zheng Yan, Chen Xianlan, Liu Yuhan, Wu Leilei, Xie Yufeng, Ju Sheng, Chen Jun, Ding Cheng, Li Chang, Tong Xin, Liu Mi, Zhao Jun
Institute of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu, 215123, P. R. China.
Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, 215123, P. R. China.
Adv Sci (Weinh). 2025 Jan;12(2):e2409913. doi: 10.1002/advs.202409913. Epub 2024 Nov 5.
Cancer involves tumor cells and tumor-specific immunity. The ability to accurately quantify tumor-specific immunity is limited. Most immunotherapies function by activating new effector tumor antigen-specific T cells (ETASTs) or reactivating the pre-existing ETASTs repertoire. Therefore, the amount of ETASTs can be used to characterize immunotherapy efficacy. Tumor antigens are highly heterogeneous and detecting most ETASTs is challenging. Therefore, nanoparticles loading whole-cell tumor antigens are used to activate and detect pan-clones ETASTs in the blood. The differences between ETASTs and other T cells are transformed into activated and non-activated states. By measuring markers of the activated status and cytotoxic function of ETASTs, it can distinguish ETASTs from other T cells. ETASTs in patients with lung cancer are higher than those in healthy individuals and those with benign pulmonary nodules. Therapeutic efficacy positively correlated with the number of ETASTs in the blood. ETATS levels increase only in the blood of patients who respond to immunotherapy. Single-cell sequencing studies validated these findings. This study provides a highly accurate, specific, non-invasive, and efficient biomarker for predicting immunotherapy efficacy in lung and other cancers. This method can also be applied to evaluate the efficacy of other treatments, such as radiotherapy, oncolytic viruses, and nanomedicine-based therapies.
癌症涉及肿瘤细胞和肿瘤特异性免疫。准确量化肿瘤特异性免疫的能力有限。大多数免疫疗法通过激活新的效应肿瘤抗原特异性T细胞（ETASTs）或重新激活预先存在的ETASTs库来发挥作用。因此，ETASTs的数量可用于表征免疫疗法的疗效。肿瘤抗原高度异质性，检测大多数ETASTs具有挑战性。因此，负载全细胞肿瘤抗原的纳米颗粒用于激活和检测血液中的泛克隆ETASTs。ETASTs与其他T细胞之间的差异转化为激活状态和未激活状态。通过测量ETASTs激活状态和细胞毒性功能的标志物，可以将ETASTs与其他T细胞区分开来。肺癌患者的ETASTs高于健康个体和良性肺结节患者。治疗效果与血液中ETASTs数量呈正相关。ETATS水平仅在对免疫疗法有反应的患者血液中升高。单细胞测序研究验证了这些发现。本研究为预测肺癌和其他癌症的免疫疗法疗效提供了一种高度准确、特异、无创且高效的生物标志物。该方法还可用于评估其他治疗方法的疗效，如放疗、溶瘤病毒和基于纳米医学的疗法。
