Reprograming the tumor immunologic microenvironment using neoadjuvant chemotherapy in osteosarcoma
Reprograming the tumor immunologic microenvironment using neoadjuvant chemotherapy in osteosarcoma
复制标题
使用骨肉瘤新辅助化疗重新编程肿瘤免疫微环境
DOI：
10.1111/cas.14398
复制
发表时间：
2020-04-23
期刊：
影响因子：
5.7
通讯作者：
Wang, Jin
中科院分区：
文献类型：
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作者：
Deng, Chuangzhong;Xu, Yanyang;Wang, Jin
肿瘤浸润性免疫细胞在肿瘤进展和治疗反应中起着至关重要的作用。然而，对浸润性免疫细胞的有限研究表明骨肉瘤(OS)的治疗结果不一致，甚至有争议。此外，新辅助化疗后浸润性免疫细胞的动态变化在很大程度上是未知的。我们从目标数据库下载了80例OS患者的RNA表达矩阵和临床信息。CiberSort用于基于基因表达数据评估患者中22种免疫细胞类型的比例。M2巨噬细胞是最丰富的免疫细胞类型，与OS患者的存活率提高有关。另一组经处理的OS样本通过免疫组织化学方法进行评估，以验证CiberSort分析的结果。收集27例患者配对的活检和手术标本，观察新辅助化疗前后免疫细胞和免疫因子的动态变化。新辅助化疗与CD3+T细胞、CD8+T细胞、Ki67+CD8+T细胞和PD-L1+免疫细胞密度升高有关。此外，治疗后人类白细胞抗原-DR-CD33+髓系抑制细胞(MDSC)明显减少。我们认为化疗的应用可能会激活局部免疫状态，将OS转化为免疫“热”瘤。这些发现为在未来的临床试验中研究OS患者的免疫治疗方案提供了理论依据。
Tumor-infiltrating immune cells play a crucial role in tumor progression and response to treatment. However, the limited studies on infiltrating immune cells have shown inconsistent and even controversial results for osteosarcoma (OS). In addition, the dynamic changes of infiltrating immune cells after neoadjuvant chemotherapy are largely unknown. We downloaded the RNA expression matrix and clinical information of 80 OS patients from the TARGET database. CIBERSORT was used to evaluate the proportion of 22 immune cell types in patients based on gene expression data. M2 macrophages were found to be the most abundant immune cell type and were associated with improved survival in OS. Another cohort of pretreated OS samples was evaluated by immunohistochemistry to validate the results from CIBERSORT analysis. Matched biopsy and surgical samples from 27 patients were collected to investigate the dynamic change of immune cells and factors before and after neoadjuvant chemotherapy. Neoadjuvant chemotherapy was associated with increased densities of CD3+ T cells, CD8+ T cells, Ki67 + CD8+ T cells and PD-L1+ immune cells. Moreover, HLA-DR-CD33+ myeloid-derived suppressive cells (MDSC) were decreased after treatment. We determined that the application of chemotherapy may activate the local immune status and convert OS into an immune "hot" tumor. These findings provide rationale for investigating the schedule of immunotherapy treatment in OS patients in future clinical trials.