免疫疗法为肺腺癌（LUAD）的治疗带来了重大进展，但确定合适的候选疗法仍然具有挑战性。在这项研究中，我们使用大量的单细胞数据研究了肿瘤细胞异质性，并探讨了 POPLAR 和 OAK 免疫治疗队列中不同肿瘤细胞簇丰度对免疫治疗的影响。值得注意的是，我们发现 CKS1B 肿瘤细胞丰度与治疗反应以及干细胞潜力之间存在显着相关性。利用 CKS1B 肿瘤细胞簇的标记基因，我们采用机器学习算法来建立 LUAD 的预后和免疫治疗特征 (PIS)。在多个队列中，PIS 在预测 LUAD 预后方面优于之前发布的 144 个特征。重要的是，PIS 可靠地预测了基因组改变、化疗敏感性和免疫治疗反应。免疫组织化学验证了低 PIS 组中免疫标记物的表达较低，而体外实验强调了关键基因 PSMB7 在 LUAD 进展中的作用。总之，PIS 代表了一种新型生物标志物，有助于选择合适的 LUAD 患者进行免疫治疗，最终改善预后并指导临床决策。© 2024 作者。北京干细胞与再生医学研究院和John Wiley联合出版的《细胞增殖》

Immunotherapy has brought significant advancements in the treatment of lung adenocarcinoma (LUAD), but identifying suitable candidates remains challenging. In this study, we investigated tumour cell heterogeneity using extensive single-cell data and explored the impact of different tumour cell cluster abundances on immunotherapy in the POPLAR and OAK immunotherapy cohorts. Notably, we found a significant correlation between CKS1B+ tumour cell abundance and treatment response, as well as stemness potential. Leveraging marker genes from the CKS1B+ tumour cell cluster, we employed machine learning algorithms to establish a prognostic and immunotherapeutic signature (PIS) for LUAD. In multiple cohorts, PIS outperformed 144 previously published signatures in predicting LUAD prognosis. Importantly, PIS reliably predicted genomic alterations, chemotherapy sensitivity and immunotherapy responses. Immunohistochemistry validated lower expression of immune markers in the low-PIS group, while in vitro experiments underscored the role of the key gene PSMB7 in LUAD progression. In conclusion, PIS represents a novel biomarker facilitating the selection of suitable LUAD patients for immunotherapy, ultimately improving prognosis and guiding clinical decisions.© 2024 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.