Wang Jin, Zeng Weibiao, Xue Jiao, Zhu Ao, Chen Xianlan, Zheng Yan, Liu Yuhan, Qin Songbing, Zhao Jun, Liu Mi
Department of Pharmaceutics, College of Pharmaceutical Science, Soochow University, Suzhou, Jiangsu 215123, People's Republic of China.
Institute of Minimally Invasive Thoracic Cancer Therapy and Translational Research, Soochow University, Suzhou, Jiangsu 215123, People's Republic of China.
Anal Chem. 2024 Dec 3;96(48):19056-19065. doi: 10.1021/acs.analchem.4c04049. Epub 2024 Nov 19.
Cancer is the result of the interactions between tumor cells and tumor-specific immune responses. The current biomarkers detect tumor cells' properties, but accurate measurement of tumor-specific immunity is lacking. Most immunotherapies work by activating new effector tumor antigen-specific T cells (ETASTs) or reactivating pre-existing ETASTs' repertoire. The responses to immunotherapy depend on the increase of ETASTs. The amount of ETASTs, especially in blood, is critical for therapeutic efficacy. Distinguishing ETASTs from other T cells by their structural characteristics is difficult. Therefore, nanoparticles loading whole tumor antigens are utilized to activate broad clones ETASTs pre-existing in peripheral blood, followed by detecting them. Thus, the differences between ETASTs and other T cells are transformed to the differences between activated states and unactivated states. By measuring the markers of activated states and cytotoxic functions, we can distinguish ETASTs from other T cells. Nanoparticles loading mixed multiple allogeneic tumor tissue lysates or mixed multiple tumor cell lines can be utilized as universal nanoparticles to replace nanoparticles loading personalized tumor tissue. ETASTs (TATAN-activated CD8IFN-γ) in esophageal cancer patients are more than those in healthy people. Measurement of the ETASTs in the blood of esophageal cancer patients before and after ongoing therapy showed that ETATSs increased in the blood of patients who were responsive to immunotherapy but did not increase in the blood of nonresponders. These illustrated that therapeutic efficacy was positively correlated with the level of ETASTs in PBMC. Altogether, this study provides us a highly accurate and specific biomarker for predicting the therapeutic efficacy of cancer immunotherapy and potentially other therapies, such as radiotherapy.
癌症是肿瘤细胞与肿瘤特异性免疫反应相互作用的结果。目前的生物标志物可检测肿瘤细胞的特性，但缺乏对肿瘤特异性免疫的准确测量。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。对免疫疗法的反应取决于ETASTs的增加。ETASTs的数量，尤其是血液中的数量，对治疗效果至关重要。通过结构特征将ETASTs与其他T细胞区分开来很困难。因此，利用负载整个肿瘤抗原的纳米颗粒来激活外周血中预先存在的广泛克隆的ETASTs，然后对其进行检测。这样，ETASTs与其他T细胞之间的差异就转化为激活状态与未激活状态之间的差异。通过测量激活状态和细胞毒性功能的标志物，我们可以将ETASTs与其他T细胞区分开来。负载混合多种同种异体肿瘤组织裂解物或混合多种肿瘤细胞系的纳米颗粒可作为通用纳米颗粒来替代负载个性化肿瘤组织的纳米颗粒。食管癌患者中的ETASTs（TATAN激活的CD8IFN-γ）比健康人更多。对正在接受治疗的食管癌患者血液中的ETASTs进行测量发现，对免疫疗法有反应的患者血液中的ETATSs增加，而无反应者血液中的ETASTs没有增加。这些表明治疗效果与外周血单个核细胞中ETASTs的水平呈正相关。总之，这项研究为我们提供了一种高度准确和特异的生物标志物，用于预测癌症免疫疗法以及潜在的其他疗法（如放射疗法）的治疗效果。
