Identification of unanimous immune subtypes for different hormone receptor phenotypes of human breast cancer with potential prognostic significance

The immunogenicity of the breast tumor microenvironment is clinically heterogeneous. The insight into the role of tumor-infiltrating lymphocytes (TILs) might serve as a biomarker to predict a survival benefit and enable optimal patient selection for immunotherapy. In this study, we aimed at characterizing the breast cancer immune subtypes linked to CD8 T cells and associating with the patient characteristics and clinical outcomes. We analyzed the immune gene signatures of human breast cancer using The Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) database profiling of 1092 breast tumor patients. We performed hierarchical clustering to the immune gene expression by applying hormone receptor status including triple negative breast cancer to categorize 66 immune-related genes in breast tumors. The separation was characterized by dividing the breast tumors into two major immune subtypes: predominant immune (PI) subtype and low immune subtype (LI). Our results showed that both PI and LI subtypes can be observed in the different hormone receptor phenotypes of breast tumors, and PI subtype accounted for 16% and LI subtype 20% in the breast tumor patients. The estimated odds for LI subtype breast tumors were significantly higher than PI subtype breast tumors in primary tumor stages. Our data demonstrated that the PI subtype breast tumors have significantly improved survival compared with LI subtype. Our findings provide a novel perspective of breast cancer immune subtypes linked to CD8 T cells. The immune subtypes will be a valuable resource for future research to identify clinically relevant biomarkers for precision immunotherapy.

Automated summary

The immunogenicity of the breast tumor microenvironment is clinically heterogeneous, with two major immune subtypes, predominant immune (PI) and low immune (LI), identified in this study. These subtypes are associated with different hormone receptor phenotypes in breast tumors, with PI subtype showing significantly improved survival compared to LI subtype. These findings highlight the potential of using immune subtypes as biomarkers for precision immunotherapy.