Sibilio Pasquale, Zizzari Ilaria Grazia, Gelibter Alain, Siringo Marco, Tuosto Lucrezia, Pace Angelica, Asquino Angela, Valentino Flavio, Sabatini Arianna, Petti Manuela, Bellati Filippo, Santini Daniele, Nuti Marianna, Farina Lorenzo, Rughetti Aurelia, Napoletano Chiara
Department of Computer, Control and Management Engineering, Sapienza University of Rome, 00161 Rome, Italy.
Laboratory of Tumor Immunology and Cell Therapies, Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy.
Cancers (Basel). 2025 Mar 8;17(6):922. doi: 10.3390/cancers17060922.
Non-small cell lung cancer (NSCLC) patients without gene driver mutations receive anti-PD1 treatments either as monotherapy or in combination with chemotherapy based on PD-L1 expression in tumor tissue. Anti-PD1 antibodies target various immune system components, perturbing the balance between immune cells and soluble factors. In this study, we identified the immune signatures of NSCLC patients associated with different clinical outcomes through network analysis. : Twenty-seven metastatic NSCLC patients were assessed at baseline for the levels of circulating CD137 T cells (total, CD4, and CD8) via cytofluorimetry, along with 14 soluble checkpoints and 20 cytokines through Luminex analysis. Hierarchical clustering and connectivity heatmaps were executed, analyzing the response to therapy (R vs. NR), performance status (PS = 0 vs. PS > 0), and overall survival (OS < 3 months vs. OS > 3 months). The clustering of immune checkpoints revealed three groups with a significant differential proportion of six checkpoints between patients with PS = 0 and PS > 0 ( < 0.0001). Furthermore, significant pairwise correlations among immune factors evaluated in R were compared to the lack of significant correlations among the same immune factors in NR patients and vice versa. These comparisons were conducted for patients with PS = 0 vs. PS > 0 and OS < 3 months vs. OS > 3 months. The results indicated that NR with PS > 0 and OS ≤ 3 months exhibited an inflammatory-specific signature compared to the contrasting clinical conditions characterized by a checkpoint molecule-based network ( < 0.05). Identifying various connectivity immune profiles linked to response to therapy, PS, and survival in NSCLC patients represents significant findings that can optimize therapeutic choices.
无基因驱动突变的非小细胞肺癌（NSCLC）患者根据肿瘤组织中的PD-L1表达情况，接受抗PD1治疗，可采用单药治疗或与化疗联合使用。抗PD1抗体靶向多种免疫系统成分，扰乱免疫细胞与可溶性因子之间的平衡。在本研究中，我们通过网络分析确定了与不同临床结果相关的NSCLC患者的免疫特征。对27例转移性NSCLC患者在基线时通过细胞荧光分析评估循环CD137 T细胞（总数、CD4和CD8）水平，同时通过Luminex分析评估14种可溶性检查点和20种细胞因子。执行层次聚类和连接热图分析，分析治疗反应（R与NR）、体能状态（PS = 0与PS > 0）和总生存期（OS < 3个月与OS > 3个月）。免疫检查点的聚类显示，在PS = 0和PS > 0的患者之间，有三组六个检查点的比例存在显著差异（< 0.0001）。此外，比较了R组中评估的免疫因子之间显著的成对相关性与NR组中相同免疫因子之间缺乏显著相关性的情况，反之亦然。对PS = 0与PS > 0以及OS < 3个月与OS > 3个月的患者进行了这些比较。结果表明，与以检查点分子为基础的网络所表征的对比临床情况相比，PS > 0且OS ≤ 3个月的NR患者表现出炎症特异性特征（< 0.05）。识别与NSCLC患者的治疗反应、PS和生存相关的各种连接性免疫谱是重要发现，可优化治疗选择。
