AKT2 for Modifying the Tumor Immune Microenvironment in Lung Adenocarcinoma.

BACKGROUND

The phosphatidylionsitol 3-kinase (PI3K)-v-akt murine thymoma viral oncogene homolog (AKT)-mammalian target of rapamycin (mTOR) pathway has been extensively studied in lung adenocarcinomas (LUAD). This study aimed to explore the correlation between this pathway and the tumor microenvironment.

METHODS

Data from the Cancer Genome Atlas (TCGA) was utilized to analyze variations in the expression of v-akt murine thymoma viral oncogene homolog 2 (AKT2) between LUAD tissues and normal tissues and to assess its effect on the survival of patients. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed. The "R language" was used to analyze the disparity between immune cell infiltration in tumor tissues and the correlation with AKT2 expression levels.

RESULTS

AKT2 was significantly upregulated in LUAD. The high expression level of AKT2 was significantly associated with shorter overall survival. Gene Set Enrichment Analysis revealed that tumor immune-related pathways such as adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin super-family domains were more active in the AKT2 high expression group. Tumor tissues with high AKT2 expression tended to have higher levels of regulatory T cells (Tregs) and CD8+ T cells and lower levels of activated dendritic cells and γδT cells. AKT2 expression was positively influenced by common immune checkpoints and correlated with TMB, suggesting that high AKT2 expression in LUAD may lead to significant immune evasion.

CONCLUSIONS

Tumor microenvironment in high AKT2 expression patients demonstrated immunosuppressive characteristics such as reduced γδT cells aggregation and increased Tregs infiltration.