Liu Yun, Lin Yunhua, Liao Shijie, Feng Wenyu, Liu Jianhong, Luo Xiaoting, Wei Qingjun, Tang Haijun
Department of Spine and Osteopathic Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Department of Trauma Orthopedic and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Heliyon. 2023 Dec 11;10(1):e23601. doi: 10.1016/j.heliyon.2023.e23601. eCollection 2024 Jan 15.
Chemotherapy, a primary treatment for osteosarcoma (OS), has limited knowledge regarding its impact on tumor immune microenvironment (TIME). Here, tissues from 6 chemotherapy-naive OS patients underwent single-cell RNA sequencing (scRNA-seq) and were analyzed alongside public dataset (GSE152048) containing 7 post-chemotherapy OS tissues. CD45 (PTPRC+) cells were used for cell clustering and annotation. Changes in immune cell composition pre- and post-chemotherapy were characterized. Totally, 28,636 high-quality CD45 (PTPRC+) cells were extracted. Following chemotherapy, the proportions of regulatory T cells (Tregs) and activated CD8 T cells decreased, while CD8 effector T cells increased. GO analysis indicated that differentially expressed genes (DEGs) in T cells were associated with cell activation, adaptive immune response, and immune response to tumor cells. Furthermore, the proportions of plasma cells increased, while naive B cells decreased. B cell surface receptors expression was upregulated, and GO analysis revealed DEGs of B cells were mainly enriched in B cell-mediated immunity and B cell activation. Moreover, M2 polarization of macrophages was suppressed post-chemotherapy. Overall, this study elucidates chemotherapy remodels the OS TIME landscape, triggering immune heterogeneity and enhancing anti-tumor properties.
化疗作为骨肉瘤（OS）的主要治疗方法，对其对肿瘤免疫微环境（TIME）的影响了解有限。在此，对6例未经化疗的OS患者的组织进行了单细胞RNA测序（scRNA-seq），并与包含7例化疗后OS组织的公共数据集（GSE152048）一起进行分析。使用CD45（PTPRC+）细胞进行细胞聚类和注释。对化疗前后免疫细胞组成的变化进行了表征。总共提取了28,636个高质量的CD45（PTPRC+）细胞。化疗后，调节性T细胞（Tregs）和活化的CD8 T细胞比例降低，而CD8效应T细胞增加。基因本体（GO）分析表明，T细胞中差异表达基因（DEGs）与细胞活化、适应性免疫反应以及对肿瘤细胞的免疫反应相关。此外，浆细胞比例增加，而幼稚B细胞比例降低。B细胞表面受体表达上调，GO分析显示B细胞的DEGs主要富集于B细胞介导的免疫和B细胞活化。此外，化疗后巨噬细胞的M2极化受到抑制。总体而言，本研究阐明了化疗重塑了OS的TIME格局，引发免疫异质性并增强抗肿瘤特性。
