Abstract
Plasmacytoid dendritic cells (pDC) are an essential immune microenvironment component. They have been reported for crucial roles in linking the adaptive and immune systems. However, the prognostic role of the pDC in breast cancer (BRCA) was controversial. In this work, we collected large sample cohorts and did a comprehensive investigation to reveal the relationship between pDC and BRCA by multiomics data analysis. Elevated pDC levels were correlated with prolonged survival outcomes in BRCA patients. The distinct mutation landscape and lower burden of somatic copy number alterations (SCNA) and lower intratumoral heterogeneity were observed in the high pDC abundance group. Additionally, a more sensitive immune response and chemotherapies response were observed in the high pDC group, which implicates that patients with high pDC abundance can be benefited from the combination of chemotherapy and immunotherapy. In conclusion, the correlation between pDC abundance and BRCA patients’ overall survival (OS) was found to be positive. We identified the molecular profiles of BRCA patients with pDC abundance. Our findings may be beneficial in aiding in the development of immunotherapy and elucidating on the precision treatment for BRCA.
Highlights
Breast cancer (BRCA) is a pathological state in which breast epithelial cells proliferate out of control under the action of multiple carcinogens
The survival analysis suggested that the abundance of the Plasmacytoid dendritic cells (pDC) was strongly positively associated with patient’s clinical outcome, which means that the elevated abundance of the pDC benefited the survival outcomes of BRCA patients included in The Cancer Genome Atlas (TCGA) cohorts (Figure 2B)
The results showed that the pDChigh group was enriched with immune-related pathways, such as T cells, B cells, natural killer (NK) cells, programmed deathligand 1 (PD-L1), chemokines, and tumor necrosis factor (TNF) signaling pathways, and biological processes, such as activation of immune response, T cell activation, and adaptive immune responses, whereas the pDClow group was enriched with cellular senescence, cell cycle, renal cell carcinoma, and several metabolic processes (Figures 3C–F)
Summary
Breast cancer (BRCA) is a pathological state in which breast epithelial cells proliferate out of control under the action of multiple carcinogens. The International Agency for Research on Cancer (IARC) documented that in 2018, BRCA has an incidence rate of 24.2% among females globally and is the most susceptible malignant tumor for women. The overall survival (OS) for early BRCA patients continues to increase, the vast majority of advanced BRCA. Breast Cancer Immune Microenvironment patients cannot be cured. The Food and Drug Administration (FDA) has approved several tumor immunotherapy drugs for clinical application (Riley et al, 2019). Immunotherapy has been used for advanced BRCA, but only for specific subtypes, such as programmed deathligand 1 (PD-L1) monoclonal antibody atezolizumab for triplenegative BRCA. Phase III clinical studies have confirmed that the combination of chemotherapy and immunotherapy can improve the curative effect and improve the OS (Schmid et al, 2018)
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