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 CD8⁺IFN-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.

中文翻译：

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免疫疗法的高效生物标志物：测量食管癌患者血液中的广义克隆效应肿瘤抗原特异性 T 细胞


癌症是肿瘤细胞与肿瘤特异性免疫反应之间相互作用的结果。目前的生物标志物检测肿瘤细胞的特性，但缺乏对肿瘤特异性免疫力的准确测量。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 （ETAST） 或重新激活预先存在的 ETAST 库来发挥作用。对免疫治疗的反应取决于 ETASTs 的增加。ETAST 的数量，尤其是血液中的 ETAST 数量，对于治疗效果至关重要。通过结构特征区分 ETAST 与其他 T 细胞是很困难的。因此，利用加载全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 ETASTs，然后检测它们。因此，ETASTs 和其他 T 细胞之间的差异被转化为活化状态和未活化状态之间的差异。通过测量活化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。纳米颗粒加载混合的多个同种异体肿瘤组织裂解物或混合的多个肿瘤细胞系可用作通用纳米颗粒，以替代加载个性化肿瘤组织的纳米颗粒。食管癌患者的 ETASTs（TATAN 激活的 CD8⁺IFN-γ⁺）多于健康人。对食管癌患者在持续治疗前后血液中 ETASTs 的测量表明，对免疫治疗有反应的患者血液中的 ETATS 增加，但在无反应者血液中没有增加。这些表明治疗效果与 PBMC 中 ETASTs 的水平呈正相关。 总而言之，这项研究为我们提供了一种高度准确和特异性的生物标志物，用于预测癌症免疫疗法和潜在的其他疗法（如放疗）的治疗效果。