Regulation and characterization of tumor-infiltrating immune cells in breast cancer

Abstract

The effect of immunosuppression blockade therapies depends on the infiltration of effector T cells and other immune cells in tumor. However, it is unclear how molecular pathways regulate the infiltration of immune cells, as well as how interactions between tumor-infiltrating immune cells and T cell activation affect breast cancer patient survival. CIBERSORT was used to estimate the relative abundance of 22 immune cell types. The association between mRNAs and immune cell abundance were assessed by Spearman correlation analysis. Enriched pathways were identified using MetaCore pathway analysis. The interactions between the T cell activation status and the abundance of tumor-infiltrating immune cells were evaluated using Kaplan-Meier survival and multivariate Cox regression models in a publicly available dataset of 1081 breast cancer patients. The role of tumor-infiltrating B cells in antitumor immunity, immune response of T cell subsets, and breakdown of CD4⁺ T cell peripheral tolerance were positively associated with M1 macrophage and CD8⁺ T cell but negatively associated with M2 macrophage. Abundant plasma cell was associated with prolonged survival (HR = 0.46, 95% CI: 0.32-0.67), and abundant M2 macrophage was associated with shortened survival (HR = 1.78, 95% CI: 1.23-2.60). There exists a significant interaction between the T cell activation status and the resting DC abundance level (p = 0.025). Molecular pathways associated with tumor-infiltrating immune cells provide future directions for developing cancer immunotherapies to control immune cell infiltration, and further influence T cell activation and patient survival in breast cancer.

Keywords: Breast cancer; Cancer survival; Molecular pathway; T cell activation score; Tumor-infiltrating immune cell.