{“_”：“BAG3 CAF-T细胞邻近预测NSCLC对新辅助化学免疫疗法的耐药性。”，“sup”：[“+”]}
{"_":"BAG3 CAF-T cell neighborhood predicts resistance to neoadjuvant chemoimmunotherapy in NSCLC.","sup":["+"]}
摘要(中文译文)
尽管新辅助化学免疫治疗（NCIT）显著改善了非小细胞肺癌（NSCLC）的预后，但仍有超过40%的患者未能达到主要病理缓解（MPR）。因此，在治疗开始前早期识别无应答者仍是亟待满足的关键临床需求。本研究对治疗前NSCLC组织样本进行了单细胞RNA测序（scRNA-seq），并整合了两个公共数据库的数据，以识别与治疗反应不佳相关的信号通路。随后使用多重免疫荧光（mIF）对关键发现进行了验证，并最终在我们的队列和GEO数据集中评估了所识别分子的预测价值。在83例患者中，23/57（40.35%）的影像学应答者未能达到MPR。数据分析显示，nMPR患者的癌症相关成纤维细胞（CAFs）和T细胞中应激相关信号通路被激活，应激相关标志物（包括BAG3和IFITM2）表达升高。mIF证实BAG3IFITM2 CAFs与BAG3CD8 T细胞在空间上相邻，且在nMPR患者中显著更丰富。在我们的队列和两个公共数据库中，BAG3 CAF-T细胞邻域在nMPR组中显著比MPR组更丰富（<0.05）。在MPR组中，影像学PR亚组与非PR亚组之间的BAG3 CAF-T细胞邻域无显著差异。BAG3IFITM2 CAFs、BAG3CD8 T细胞和BAG3 CAF-T细胞邻域的AUC值分别为0.84 [95%CI：0.746-0.931]、0.72 [95%CI：0.603-0.835]和0.87 [95%CI：0.787-0.948]。BAG3 CAF-T细胞邻域高组的OS和DFS显著低于低组（<0.05）。BAG3 CAF-T细胞邻域水平在预测NCIT无应答方面优于其他两项指标。在GSE126044和GSE135222中观察到一致的结果。BAG3 CAF-T细胞邻域可作为预测NSCLC患者NCIT无应答的生物标志物，具有指导临床决策的重要潜力。
Abstract
Despite significantly improving outcomes in non-small cell lung cancer (NSCLC), neoadjuvant chemoimmunotherapy (NCIT) fails to achieve a major pathological response (MPR) in over 40% of patients. Consequently, the early identification of non-responders prior to treatment initiation remains a critical unmet clinical need. In this study, we performed single-cell RNA sequencing (scRNA-seq) on pre-treatment NSCLC tissue samples and integrated data from two public databases to identify signaling pathways associated with poor treatment response. Key findings were subsequently validated using multiplex immunofluorescence (mIF), and the predictive value of identified molecules was finally assessed in our cohort and GEO datasets. Among the 83 patients, 23/57 (40.35%) of these radiological responders failed to achieve MPR. Data analysis revealed activation of stress-related signaling pathways in cancer-associated fibroblasts (CAFs) and T cells from nMPR patients, with elevated expression of stress-related markers, including BAG3 and IFITM2. MIF confirmed that BAG3IFITM2 CAFs and BAG3CD8 T cells were spatially adjacent and significantly more abundant in nMPR patients. In our cohort and the two public databases, the BAG3 CAF-T Cell Neighborhood was significantly more abundant in the nMPR group compared to the MPR group (<0.05). In the MPR group, there was no significant difference in BAG3 CAF-T Cell Neighborhood between the radiological PR and non-PR subgroups. The AUC values of BAG3IFITM2 CAFs, BAG3CD8 T cells, and the BAG3 CAF-T Cell Neighborhood were 0.84 [95%CI: 0.746-0.931], 0.72 [95%CI: 0.603-0.835], and 0.87 [95%CI: 0.787-0.948], respectively. The OS and DFS of the BAG3 CAF-T Cell Neighborhood high group are significantly decreased than that of the low group (<0.05). The level of BAG3 CAF-T Cell Neighborhood outperformed other two indicators in predicting non-response to NCIT. Consistent results were observed in GSE126044 and GSE135222. The BAG3 CAF-T Cell Neighborhood may serve as a biomarker for predicting non-response to NCIT in NSCLC, with significant potential to inform clinical decision-making.
如何引用
AMA
Jing Sun, Zhengqi Cao, Yueping Jin, Anni Wang, Li Lu, Lixuan Chen, et al. {"_":"BAG3 CAF-T cell neighborhood predicts resistance to neoadjuvant chemoimmunotherapy in NSCLC.","sup":["+"]}. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1823199.
APA
Jing Sun, Zhengqi Cao, Yueping Jin, Anni Wang, Li Lu, Lixuan Chen, et al (2026). {"_":"BAG3 CAF-T cell neighborhood predicts resistance to neoadjuvant chemoimmunotherapy in NSCLC.","sup":["+"]}. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1823199
GB/T 7714
Jing Sun, Zhengqi Cao, Yueping Jin, Anni Wang, Li Lu, Lixuan Chen, et al. {"_":"BAG3 CAF-T cell neighborhood predicts resistance to neoadjuvant chemoimmunotherapy in NSCLC.","sup":["+"]}[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1823199.
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