Immune Landscape of the Tumor Microenvironment Identifies Prognostic Gene Signature CD4/CD68/CSF1R in Osteosarcoma
Immune Landscape of the Tumor Microenvironment Identifies Prognostic Gene Signature CD4/CD68/CSF1R in Osteosarcoma
复制标题
肿瘤微环境的免疫景观识别骨肉瘤中的预后基因特征 CD4/CD68/CSF1R
DOI：
10.3389/fonc.2020.01198
复制
发表时间：
2020-07-24
影响因子：
4.7
通讯作者：
Wang, Jin
中科院分区：
文献类型：
--
作者：
Song, Yi-jiang;Xu, Yanyang;Wang, Jin
背景：骨肉瘤（OSA）是儿童和青少年最常见的原发性骨恶性肿瘤，容易发生转移，预后不良。由于其强烈的基因组异质性，传统化疗或靶向免疫治疗几十年来未能有效改善相关的总生存率。尽管 OSA 肿瘤免疫微环境在预测临床结果和治疗效果方面发挥着至关重要的作用，但由于人们对 OSA 肿瘤免疫微环境的情况知之甚少，我们的目的是阐明其分子特征。方法：使用转录组分析和从治疗应用研究生成有效治疗 (TARGET) 计划中检索的临床特征来探索 101 个 OSA 样本的免疫特征。基于 45 个 OSA 原发肿瘤评估和验证了预后免疫标志物与其临床化疗反应之间的相关性。研究结果：我们确定了 OSA 中肿瘤免疫特征的异质性，并发现 CD4+ T 细胞和巨噬细胞标记物 CD4/IFNGR2/CD68 是可行的预后因素，彼此之间具有显着的正相关性。具体而言，CSF1R 在巨噬细胞增殖和分化的调节中发挥重要作用，被发现是与 CD4/CD68 相关的特定特征，可改善 OSA 临床结果。解释：基于 CD4/CD68/CSF1R 基因特征的免疫景观对于 OSA 患者的预后和治疗分层显示出相当大的前景。 OSA 的特异性免疫特征主要由 Th1 极化 CD4+ T 细胞和 CSF1R 相关 CD68+ 巨噬细胞组成，可以提高化疗的预测效果并改善 OSA 患者的预后。
Background: Osteosarcoma (OSA), the most common primary bone malignancy in children and adolescents, is prone to metastases and unfavorable prognosis. Owing to its strong genomic heterogeneity, traditional chemotherapy, or targeted immunotherapy has not effectively improved the related overall survival for decades. Since the landscape of the OSA tumor immune microenvironment is scarcely known, despite it playing a crucial role in predicting clinical outcomes and therapeutic efficacies, we aimed to elucidate its molecular characteristics. Methods: The immune signature of 101 OSA samples was explored using transcriptome profiling and clinical characteristics retrieved from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) program. Correlations between the prognostic immune markers and their clinical chemotherapy responses were assessed and verified based on 45 OSA primary tumors. Findings: We identified the heterogeneity underlying tumor immune signature in OSA, and found CD4+ T cells and macrophage markers CD4/IFNGR2/CD68 to be feasible prognostic factors, exerting significantly positive correlation with each other. Specifically, CSF1R, which plays an essential role in the regulation of proliferation and differentiation of macrophages, was found to be a specific signature associated with CD4/CD68, with improved OSA clinical outcomes. Interpretation: The immune landscape based on CD4/CD68/CSF1R gene signatures showed considerable promise for prognostic and therapeutic stratification in OSA patients. A specific immune signature for OSA, abundantly consisting of Th1-polarized CD4+ T cells and CSF1R-related CD68+ macrophages, may improve the predictive efficacy of chemotherapy and improve prognosis in patients with OSA.