RFTN1: an potential inhibitor of the immunity system in TME of breast cancer improving the tumor immune escape

Abstract Background Immune checkpoint inhibitors have been extensively utilized in treating breast cancer patients, leading to improved prognoses. For patients with negative checkpoint responses, there is a pressing need to identify alternative therapies to improve outcomes. Method We used WGCNA in muti-place metastasis samples to find the lymph node metastasis related gene RFTN1. Consensus cluster show the different subtype with significant pathway changes and immune cells differences. We used CellChat estimated the different interactions of cells in single cell data. We used hdWGCNA and irGSEA to identify the changes between different RFTN1expression groups. Results Our research began by analyzing RNA sequences from breast cancer tumors with metastasis using WGCNA. We identified a gene, RFTN1, that is closely associated with lymph node metastasis, a critical early step in breast cancer spread. Subsequent analysis of RFTN1's potential functions, using data from TCGA-BRCA project, suggested that RFTN1might be involved in regulating the immune system. Single-cell RNA sequencing revealed that samples with higher RFTN1expression had increased proportions of CD8+ and CD4+ T cells, albeit the overall proportions were lower. These samples also showed different interactions between T cells and other cells, indicating a greater reception of chemotactic factors (CFs) in samples with higher RFTN1 expression. Previous studies have confirmed RFTN1's role in macrophages, aligning with the pathways enriched by the differential gene expression associated with varying levels of RFTN1. It appears that RFTN1 may facilitate T cell receptor binding to CFs, thereby enhancing T cell activation in the tumor microenvironment (TME). Additionally, pathways related to apoptosis were upregulated in samples with higher RFTN1expression, correlating with a reduced proportion of malignant cells. Conclusion This study proposes a novel approach to modulating T cells in the TME and offers an alternative to traditional immune checkpoint inhibitor therapies for treating BC. RFTN1 is related to the CFs receptor transportation in CD4+ T cells and CD8+ T cells, which may activate the anti-tumor immunity system in TME.