Identification of immune subtypes to guide immunotherapy and targeted therapy in clear cell renal cell carcinoma

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.

Automated summary

This study aimed to classify and define the immune subtypes of clear cell renal cell carcinoma (ccRCC) to identify potential immunotherapy-responsive subtypes. Significant differences in immune cell infiltration, immune checkpoints, and antigens were observed between ccRCC and para-cancerous tissues. Based on immune components, ccRCC patients were divided into three immune subtypes, each with different clinical and molecular characteristics. Further analysis revealed variations in immune checkpoint expression among the subtypes, with abnormal up-regulation in one subtype (IS3). Pathway enrichment analysis identified abnormal enrichment of specific signaling pathways in each subtype. A specific antigen of ccRCC (SCG2) was associated with poor prognosis and correlated significantly with immune cells and immune checkpoints. These findings provide new insights into the tumor biology and clinical management of ccRCC.