Department of Radiation Oncology, First Hospital of China Medical University, Heping District, Shenyang,, Liaoning, China.
J Transl Med. 2021 May 10;19(1):200. doi: 10.1186/s12967-021-02845-y.
To understand the molecular mechanisms of the antitumour response, we analysed the immune landscape of cervical cancer to identify novel immune molecular classes.
We established a stable immune molecular classification using a nonnegative matrix factorization algorithm and validated the correlation in two validation sets of 249 samples.
Approximately 78% of cervical cancers (CCs) (228/293) were identified to show significant enrichment in immune cells (e.g., CD8 T cells and macrophages), a type I IFN response, enhanced cytolytic activity and high PDCD1, and these CCs were referred to as the "immune class". We further identified two subtypes of the immune class: active immune and exhausted subtypes. Although the active immune subtype was characterized by enrichment of IFN signatures and better survival, the exhausted subtype expressed activated stroma, a wound healing signature, enhanced M2 macrophages and absence of CD8 T cells and the TGF-β response signature. Integrative analysis of multiomics data identified EGFR, JUN, MYC, FN1 and SERPINE1 as key modulators of the tumour immune microenvironment and potential targets for combination therapies which was validated in two validation sets.
Our study introduces a novel immune classification that might predict ideal candidates to receive immunotherapy or specific combination therapies.
为了了解抗肿瘤反应的分子机制，我们分析了宫颈癌的免疫图谱，以确定新的免疫分子类型。
我们使用非负矩阵分解算法建立了一种稳定的免疫分子分类，并在两个包含 249 个样本的验证集中验证了相关性。
约 78%的宫颈癌（CC）（228/293）被鉴定为显著富集免疫细胞（如 CD8 T 细胞和巨噬细胞）、I 型 IFN 反应、增强的细胞毒性和高 PDCD1，这些 CC 被称为“免疫类”。我们进一步鉴定了免疫类的两种亚型：活跃免疫亚型和耗竭亚型。尽管活跃免疫亚型的特点是富含 IFN 特征，且生存率更高，但耗竭亚型表达激活的基质、伤口愈合特征、增强的 M2 巨噬细胞以及缺乏 CD8 T 细胞和 TGF-β反应特征。多组学数据的综合分析确定了 EGFR、JUN、MYC、FN1 和 SERPINE1 作为肿瘤免疫微环境的关键调节剂和潜在的联合治疗靶点，在两个验证集中得到了验证。
我们的研究提出了一种新的免疫分类，可能预测理想的免疫治疗或特定联合治疗的候选者。
