Accumulating pieces of evidence suggested that immunotypes may indicate the overall immune landscape in the tumor microenvironment, which were closely related to therapeutic response. The purpose of this study was to classify and define the immune subtypes of clear cell renal cell carcinoma (ccRCC), so as to authenticate the potential immune subtypes that respond to immunotherapy. Transcriptome expression profile and mutation profile data of ccRCC, as well as clinical characteristics used in this study were obtained from TCGA database. There were significant differences in the infiltration of immune cells, immune checkpoints, and antigens between ccRCC and para-cancerous tissues. According to immune components, patients with ccRCC were divided into three immune subtypes, with different clinical and molecular characteristics. Compared with other subtypes, IS2 showed cold immune phenotype, and was associated with better survival. IS1 represented complex immune populations and was associated with poor overall survival (OS) and progression free survival (PFS). Further analysis indicated that expression of immune checkpoints also differed among the three subtypes, and was abnormally up-regulated in IS3. Pathway enrichment analysis indicated that the mTOR signaling pathway was abnormally enriched in IS3, while the TGF_BETA, ANGIOGENESIS and receptor tyrosine kinase signaling pathways were abnormally enriched in IS2. Furthermore, there was an abnormal enrichment of the epithelial-to-mesenchymal transition (EMT) signaling pathway in IS1, which may be associated with a higher rate of metastasis. Finally, SCG2 was screened as a specific antigen of ccRCC, which was not only related to poor prognosis, but also significantly associated with immune cells and immune checkpoints. In conclusion, the immune subtypes of ccRCC may provide new insights into the tumor biology and the precise clinical management of this disease.

中文翻译：

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鉴定免疫亚型以指导透明细胞肾细胞癌的免疫治疗和靶向治疗

越来越多的证据表明，免疫类型可能表明肿瘤微环境中的整体免疫景观，这与治疗反应密切相关。本研究的目的是对透明细胞肾细胞癌 (ccRCC) 的免疫亚型进行分类和定义，以验证对免疫疗法有反应的潜在免疫亚型。ccRCC 的转录组表达谱和突变谱数据，以及本研究中使用的临床特征均来自 TCGA 数据库。ccRCC和癌旁组织在免疫细胞、免疫检查点和抗原的浸润方面存在显着差异。根据免疫成分，ccRCC患者分为三种免疫亚型，具有不同的临床和分子特征。与其他亚型相比，IS2表现出冷免疫表型，与更好的生存相关。IS1 代表复杂的免疫群体，与较差的总生存期 (OS) 和无进展生存期 (PFS) 相关。进一步分析表明，免疫检查点的表达在三种亚型之间也存在差异，并且在 IS3 中异常上调。Pathway富集分析表明，mTOR信号通路在IS3中异常富集，而TGF_BETA、ANGIOGENESIS和受体酪氨酸激酶信号通路在IS2中异常富集。此外，IS1 中的上皮-间质转化 (EMT) 信号通路异常富集，这可能与更高的转移率有关。最后筛选出SCG2作为ccRCC的特异性抗原，不仅与预后不良有关，还与免疫细胞和免疫检查点显着相关。总之，ccRCC 的免疫亚型可能为肿瘤生物学和该疾病的精确临床管理提供新的见解。