Abstract
Breast cancer (BRCA) has traditionally been considered as having poor immunogenicity and is characterized by relatively low tumor mutational burden (TMB). Improving immunogenicity may improve the response to clinical immunotherapy of BRCA. However, the relationship between TMB, immune infiltration, and prognosis in BRCA remains unclear. We aimed to explore their interrelations and potential biomarkers. In this study, based on somatic mutation data of BRCA from The Cancer Genome Atlas (TCGA), patients were categorized into high and low TMB groups utilizing the TMB values. CIBERSOFT algorithm indicated significant infiltration of activated partial immune cells in high TMB group. Besides, ADRB1 had been identified as a prognosis-related immune gene in the mutant genes by the combination of the ImmPort database and the univariate Cox analysis. ADRB1 mutation was associated with lower TMB and manifested a satisfactory clinical prognosis. Various database applications (Gene Set Enrichment Analysis, Tumor IMmune Estimation Resource, Connectivity Map, KnockTF) supported the selection of treatment strategies targeting ADRB1. In conclusion, TMB was not an independent prognostic factor for BRCA and high TMB was more likely to activate a partial immune response. ADRB1 was identified as a potential biomarker and may provide new insights for co-therapy of BRCA.
Highlights
Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) are immune checkpoint inhibitors (ICIs) [1], which is the most studied type of immunotherapy for breast cancer (BRCA) according to relevant statistics [2]
tumor mutational burden (TMB) was calculated based on the Breast cancer (BRCA) mutation data from The Cancer Genome Atlas (TCGA), and the relationship between the survival curve and TMB showed that TMB may not be an independent prognostic factor for BRCA, which is consistent with previous studies on HER2 (-) metastatic BRCA [21]
To clarify the internal relationship between TMB and immunologic infiltration, we further showed that the low TMB group had abundant levels of B cells, follicular helper T cells, gamma delta T cells, and various resting immune cells
Summary
Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) are immune checkpoint inhibitors (ICIs) [1], which is the most studied type of immunotherapy for breast cancer (BRCA) according to relevant statistics [2]. Allison and Vogelstein have reported a large number of new antigens in breast and bowel cancer tissues, and all cancers have the potential to accumulate new antigens that the immune system can recognize during tumorigenesis [14]. These findings suggest that TMB may play a predictive role in BRCA. Studies have demonstrated that the proliferation rate and the intrinsic subtype of BRCA were associated with TMB [15, 16], whose role in tumor immunogenicity in BRCA is still unclear
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