Department of Thoracic Surgery, The People's Hospital of Gaozhou, Gaozhou, China.
Guangdong Esophageal Cancer Institute, Guangzhou, China.
Ann Med. 2021 Dec;53(1):626-638. doi: 10.1080/07853890.2021.1912385.
The response rate and survival benefit of immunotherapy vary among patients, implying specific immune status of an individual could be associated with the effect of immunotherapy. However, in-depth studies of immune subtypes (ISs), immune landscape and tumour microenvironment of oesophageal cancer (ESCA) and their clinical implications are less reported.
We first accessed data from publicly available databases and preprocessed it based on a standard protocol. Then, ISs were identified by unsupervised learning. Thereafter, the association of these ISs and tumour mutation burden (TMB), biomarkers of chemotherapy-induced immune response, tumour markers were also assessed. In addition, the immune characteristics, immune landscape, co-expression network of immune genes, and clinical implications were visualized and analysed.
We identified three immunoclusters based on immune-associated genes with intra-class heterogeneity and prognostic value. Cluster-specific associations with TMB, markers of chemotherapy-induced immune response, and tumour markers were revealed. A 4-gene signature (risk score= -0.16514291×-0.03964046×-0.15242778×-0.05553572×) based on co-expressed genes in the immunoclusters was developed and externally validated.
In summary, we identified clinically relevant immunoclusters in both adenocarcinoma and squamous cell carcinoma of oesophagus, revealing the necessity of assessing the complexity and diversity of immune microenvironment for cancer immunotherapy.
免疫疗法的应答率和生存获益在患者之间存在差异，这意味着个体的特定免疫状态可能与免疫疗法的效果相关。然而，食管癌（ESCA）的免疫亚型（ISs）、免疫景观和肿瘤微环境及其临床意义的深入研究较少报道。
我们首先从公开可用的数据库中获取数据，并根据标准协议对其进行预处理。然后，通过无监督学习来识别 ISs。此后，还评估了这些 ISs 与肿瘤突变负担（TMB）、化疗诱导免疫反应的生物标志物、肿瘤标志物的相关性。此外，可视化和分析了免疫特征、免疫景观、免疫基因的共表达网络以及临床意义。
我们基于与免疫相关的基因，根据内在的异质性和预后价值，识别出三个免疫簇。揭示了簇特异性与 TMB、化疗诱导免疫反应的生物标志物和肿瘤标志物的关联。基于免疫簇中共表达基因开发了一个 4 基因特征（风险评分=-0.16514291×-0.03964046×-0.15242778×-0.05553572×），并进行了外部验证。
总之，我们在食管腺癌和鳞状细胞癌中均鉴定出了具有临床相关性的免疫簇，揭示了评估癌症免疫治疗中免疫微环境的复杂性和多样性的必要性。
