The Prognostic Value of Tumor Mutation Burden and Immune Cell Infiltration in Thymic Epithelial Tumors.

Objective: The question of whether the tumor mutation burden (TMB) is associated with either improved survival outcomes or improvement of immunotherapies remains controversial in various malignancies. The aim of this study is to investigate the genomic landscape of the relationship between TMB and immune cell infiltration in thymic epithelial tumors (TETs).

Methods: We downloaded somatic mutation data, transcriptome sequencing data, and clinical information of TETs from the Cancer Genome Atlas (TCGA) database. We assessed the abundance of 22 immune fractions between low-TMB (TMB-L) and high-TMB (TMB-H) groups using the "CIBERSORT" package.

Results: Missense mutation had the highest frequency of mutation among the nine variant classifications in TETs. Higher TMB levels were associated with poor survival outcomes (<0.05), and higher Masaoka stages (<0.05). More importantly, TMB levels were much higher in the thymic cancer than in thymoma (<0.01). The infiltration levers of naive CD4(+) T cells and regulatory T cells were significantly higher in the TMB-L group than in the TMB-H group, and this was further associated with better overall survival (OS) in patients with TETs.

Conclusion: The present study indicates that the prognosis of TMB-H patients with TETs is significantly poorer than is that of TMB-L patients, which might result from the different levels of infiltration of naive CD4(+) T cells and regulatory T cells.