Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
J Transl Med. 2022 Jul 25;20(1):332. doi: 10.1186/s12967-022-03520-6.
Except for B7-CD28 family members, more novel immune checkpoints are being discovered. They are closely associated with tumor immune microenvironment and regulate the function of many immune cells. Various cancer therapeutic studies targeting these novel immune checkpoints are currently in full swing. However, studies concerning novel immune checkpoints phenotypes and clinical significance in lung adenocarcinoma (LUAD) are still limited.
We enrolled 1883 LUAD cases from nine different cohorts. The samples from The Cancer Genome Atlas (TCGA) were used as a training set, whereas seven microarray data cohorts and an independent cohort with 102 qPCR data were used for validation. The immune profiles and potential mechanism of the system were also explored.
After univariate Cox proportional hazards regression and stepwise multivariable Cox analysis, a novel immune checkpoints-based system (LTA, CD160, and CD40LG) were identified from the training set, which significantly stratified patients into high- and low-risk groups with different survivals. Furthermore, this system has been well validated in different clinical subgroups and multiple validation cohorts. It also acted as an independent prognostic factor for patients with LAUD in different cohorts. Further exploration suggested that high-risk patients exhibited distinctive immune cells infiltration and suffered an immunosuppressive state. Additionally, this system is closely linked to various classical immunotherapy biomarkers.
we constructed a novel immune checkpoints-based system for LUAD, which predicts prognosis and immunotherapeutic implications. We believe that these findings will not only aid in clinical management but will also shed some light on screening appropriate patients for immunotherapy.
除了 B7-CD28 家族成员外，更多新的免疫检查点正在被发现。它们与肿瘤免疫微环境密切相关，调节许多免疫细胞的功能。目前，针对这些新的免疫检查点的各种癌症治疗研究正在全面展开。然而，关于肺腺癌（LUAD）中新型免疫检查点表型和临床意义的研究仍然有限。
我们从九个不同的队列中招募了 1883 例 LUAD 病例。TCGA 的样本被用作训练集，而七个微阵列数据队列和一个包含 102 个 qPCR 数据的独立队列被用于验证。还探索了系统的免疫特征和潜在机制。
经过单因素 Cox 比例风险回归和逐步多因素 Cox 分析，从训练集中确定了一个基于新型免疫检查点的系统（LTA、CD160 和 CD40LG），该系统显著地将患者分为生存率不同的高风险和低风险组。此外，该系统在不同的临床亚组和多个验证队列中得到了很好的验证。它也是不同队列中 LUAD 患者的独立预后因素。进一步的探索表明，高危患者表现出独特的免疫细胞浸润和免疫抑制状态。此外，该系统与各种经典免疫治疗生物标志物密切相关。
我们构建了一个用于 LUAD 的基于新型免疫检查点的系统，该系统可以预测预后和免疫治疗意义。我们相信这些发现不仅有助于临床管理，还将为筛选合适的免疫治疗患者提供一些启示。
