四川大学郭安源等研究人员合作开发出预测可提高免疫检查点阻断疗法疗效药物的方法。这一研究成果于2024年3月18日在线发表在国际学术期刊《自然—免疫学》上。

研究人员开发了一种名为CM-Drug的通用数据驱动方法，用于根据在免疫检查点阻断疗法（ICB）疗法中应答和非应答样本之间，识别出的核心和次要基因集筛选可提高ICB疗效的化合物。利用黑色素瘤和肺癌小鼠模型对CM-Drug方法进行了验证，9个预测化合物中有8个具有综合疗效。

在这些化合物中，他替瑞林的协同效应最强。机理分析和实验验证表明，他替瑞林能刺激CD8⁺ T细胞，并通过诱导促甲状腺激素发挥作用。这项研究为预测和评估联合疗法药物提供了一种有效的通用方法，并为未来的ICB联合疗法确定了候选化合物。

据了解，联合疗法是提高ICB疗效的一种前景广阔的治疗策略。然而，预测有效的联合疗法药物却具有挑战性。

附：英文原文

Title: A method for predicting drugs that can boost the efficacy of immune checkpoint blockade

Author: Xia, Yun, Li, Xin, Bie, Nana, Pan, Wen, Miao, Ya-Ru, Yang, Mei, Gao, Yan, Chen, Chuang, Liu, Hanqing, Gan, Lu, Guo, An-Yuan

Issue&Volume: 2024-03-18

Abstract: Combination therapy is a promising therapeutic strategy to enhance the efficacy of immune checkpoint blockade (ICB); however, predicting drugs for effective combination is challenging. Here we developed a general data-driven method called CM-Drug for screening compounds that can boost ICB treatment efficacy based on core and minor gene sets identified between responsive and nonresponsive samples in ICB therapy. The CM-Drug method was validated using melanoma and lung cancer mouse models, with combined therapeutic efficacy demonstrated in eight of nine predicted compounds. Among these compounds, taltirelin had the strongest synergistic effect. Mechanistic analysis and experimental verification demonstrated that taltirelin can stimulate CD8+ T cells and is mediated by the induction of thyroid-stimulating hormone. This study provides an effective and general method for predicting and evaluating drugs for combination therapy and identifies candidate compounds for future ICB combination therapy.

DOI: 10.1038/s41590-024-01789-x

Source: https://www.nature.com/articles/s41590-024-01789-x