Is Associated with Immune Infiltration and Immunotherapy Signatures in AML and Promotes Its Progression.

BACKGROUND

Cluster of differentiation 86 (), also known as B7-2, is a molecule expressed on antigen-presenting cells that provides the costimulatory signals required for T cell activation and survival. binds to two ligands on the surface of T cells: the antigen and cytotoxic T lymphocyte-associated protein 4 (CTLA-4). By binding to , -together with -promotes the participation of T cells in the antigen presentation process. However, the interrelationships among , immunotherapy, and immune infiltration in acute myeloid leukemia (AML) are unclear.

METHODS

The immunological effects of in various cancers (including on chemokines, immunostimulators, MHC, and receptors) were evaluated through a pan-cancer analysis using TCGA and GEO databases. The relationship between expression and mononucleotide variation, gene copy number variation, methylation, immune checkpoint blockers (ICBs), and T-cell inflammation score in AML was subsequently examined. ESTIMATE and limma packages were used to identify genes at the intersection of with StromalScore and ImmuneScore. Subsequently, GO/KEGG and PPI network analyses were performed. The immune risk score (IRS) model was constructed, and the validation set was used for verification. The predictive value was compared with the TIDE score.

RESULTS

was overexpressed in many cancers, and its overexpression was associated with a poor prognosis. expression was positively correlated with the expression of , , , , and other genes and negatively correlated with methylation. The expression of in AML cell lines was detected by QRT-PCR and Western blot, and the results showed that was overexpressed in AML cell lines. Immune infiltration assays showed that expression was positively correlated with CD8 T cell, Dendritic cell, macrophage, NK cell, and Th1_cell and also with immune examination site, immune regulation, immunotherapy response, and TIICs. ssGSEA showed that was enriched in immune-related pathways, and expression was correlated with mutations in the genes , , and , which are associated with responses to radiotherapy and chemotherapy. The IRS score performed better than the TIDE website score.

CONCLUSION

appears to participate in immune invasion in AML and is an important player in the tumor microenvironment in this malignancy. At the same time, the IRS score developed by us has a good effect and may provide some support for the diagnosis of AML. Thus, may serve as a potential target for AML immunotherapy.