Pan-cancer Analysis for the Prognostic and Immunological Role of CD47: Interact with TNFRSF9 Inducing CD8+T Cell Exhaustion.

Abstract

Abstract Purpose The role of CD47 in the effectiveness of immunotherapy has been researched. An understanding of the impact of CD47 on the tumor immune microenvironment, particularly with regard to CD8 + T cells, remains inadequately clarified. Our research focuses on investigating the prognostic and immunological significance of CD47 to gain a deeper understanding of its potential applications in immunotherapy. Methods The examination of differential gene expression, prognosis, immunological infiltration, pathway enrichment, and correlation was conducted using various R packages, computational tools, datasets, and cohorts. The notion was validated by the use of single-cell sequencing. Results CD47 was expressed in nearly all cancer types, associated with poor prognosis in pan-cancer. The immunological research revealed that CD47 exhibited a stronger correlation with T-cell infiltration as opposed to T-cell rejection in cases of multiple cancers. The cytotoxic CD8 + T cell Top group had a poorer prognosis in the CD47-high group than the CD47-low group showing CD47 might impair CD8 + T cell function. Mechanism exploration found that CD47 differential genes in multiple cancers were enriched in the CD8 + T-cell exhausted pathway. Subsequent analysis of the CD8 TCR Downstream Pathway and correlation analysis of genes further demonstrated the significant involvement of TNFRSF9. Conclusion There is a strong correlation between CD47 and the exhaustion of CD8 + T cells, which in turn can facilitate immune evasion by cancer cells, ultimately resulting in a negative prognosis. Hence, the genes CD47 and T-cell exhaustion-linked genes, particularly TNFRSF9, exhibit potential as dual antigenic targets and offer valuable insights into the realm of immunotherapy.