作为一种特别致命的恶性肿瘤，小细胞肺癌（SCLC）的治疗选择仍然有限。B7-CD28家族成员是免疫检查点阻断策略的重要靶点，该策略包括通过激活、抑制和微调T细胞免疫反应来达到治疗目的。然而，它们的临床特征和重要性尚未得到全面探究。我们招募了228名初诊为SCLC的患者，其中包括来自Cbioportal的77例和151例qPCR数据的验证队列。采用Kaplan-Meier分析和LASSO Cox模型，确定了基于B7-CD28家族的标志，用于准确预测SCLC患者的化疗效益和预后。此外，我们采用基因组学分析来探索潜在的标志相关分子机制和免疫景观。健康组织和SCLC组织的突变谱不同。确定了由七个基因（CD86、ICOSLG、CD276、CD28、CTLA-4、PDCD1和TMIGD2）组成的标志，并根据风险水平（高风险和低风险）将患者分组，产生两个生存结果显著不同的组（HR = 3.81，95％ CI：2.16-6.74，P <0.001）。基于免疫检查点的标志能够准确预测选定的训练和验证集的患者预后。值得注意的是，低风险患者更有可能从化疗中获益，并显示出更大的免疫激活。此外，时间依赖的ROC曲线和C指数分析证实，与临床识别参数相比，基于免疫检查点的标志具有出色的预测能力，用于预后和化疗效益。最后，多元分析证实，确定的标志是预后和化疗反应的独立风险因素。我们系统地获得了B7-CD28家族成员在SCLC患者中的全面分子图谱，从中产生了一个可靠和稳健的预后基于免疫检查点的标志，有潜力改善SCLC患者的预后分层和治疗策略。版权所有© 2023 Elsevier B.V. 发布。www.elsevier.com/zh-cn.

Therapeutic options for small cell lung cancer (SCLC), a particularly lethal malignancy, remain limited. Members of the B7-CD28 family are compelling targets for immune checkpoint blockade strategies, which involve activating, inhibiting, and fine-tuning the T cell immune response. However, their clinical features and significance have not been explored comprehensively.We enrolled 228 patients with an initial diagnosis of SCLC, including 77 cases from Cbioportal and a validation cohort of 151 cases with qPCR data. Kaplan-Meier analysis and LASSO Cox model were used to identify a signature based on the B7-CD28 family, which was applied for accurate prediction of chemotherapy benefit and prognosis for SCLC patients. In addition, we applied bioinformatics analysis to explore potential signature-related molecular mechanisms and the immune landscape.The mutation profiles of healthy tissues and SCLC tissues were distinct. A signature consisting of seven genes (CD86, ICOSLG, CD276, CD28, CTLA-4, PDCD1, and TMIGD2) was identified and applied to group patients based on risk level (high-risk and low-risk), producing two groups for which survival outcomes differed significantly (HR = 3.81, 95% CI: 2.16-6.74, P < 0.001). The immune checkpoint-based signature accurately predicted patient outcomes for the selected training and validation sets. Notably, low-risk patients were more likely to benefit from chemotherapy and showed greater immune activation. Additionally, time-dependent ROC curves and C-index analysis confirmed that the immune checkpoint-based signature has excellent predictive power for prognosis and chemotherapy benefit compared to clinically recognized parameters. Finally, multivariate analysis confirmed the identified signature as an independent risk factor for prognosis and chemotherapeutic response.We systematically obtained a comprehensive molecular profile for B7-CD28 family members in SCLC patients, from which we produced a reliable and robust prognostic immune checkpoint-based signature with the potential to improve prognostic stratification and therapy strategies for SCLC patients.Copyright © 2023. Published by Elsevier B.V.