Two Different Immune Profiles Are Identified in Sentinel Lymph Nodes of Early-Stage Breast Cancer.

Simple Summary: In this study, the researchers aimed to improve the prognostic information provided by the standard One-Step Nucleic Acid Amplification (OSNA) assay used to detect breast cancer (BC) metastasis in sentinel lymph nodes (SLNs). They analysed the expression of an immune gene panel in SLNs from Luminal A early-stage BC (cT1-T2 N0) patients, including those with and without subclinical metastasis. The study identified two distinct immune response profiles—one showing an adaptive anti-tumour immune response, and another with a more undifferentiated response. The researchers also identified seven key immunoregulatory genes that could serve as potential targets for immunotherapy. These findings suggest that analysing immune gene expression in SLNs can provide additional prognostic information beyond the OSNA assay results and may help guide personalised treatment approaches for early-stage BC patients. In the management of early-stage breast cancer (BC), lymph nodes (LNs) are typically characterised using the One-Step Nucleic Acid Amplification (OSNA) assay, a standard procedure for assessing subclinical metastasis in sentinel LNs (SLNs). The pivotal role of LNs in coordinating the immune response against BC is often overlooked. Our aim was to improve prognostic information provided by the OSNA assay and explore immune-related gene signatures in SLNs. The expression of an immune gene panel was analysed in SLNs from 32 patients with Luminal A early-stage BC (cT1-T2 N0). Using an unsupervised approach based on these expression values, this study identified two clusters, regardless of the SLN invasion: one evidencing an adaptive anti-tumoral immune response, characterised by an increase in naive B cells, follicular T helper cells, and activated NK cells; and another with a more undifferentiated response, with an increase in the activated-to-resting dendritic cells (DCs) ratio. Through a protein—protein interaction (PPI) network, we identified seven immunoregulatory hub genes: CD80, CD40, TNF, FCGR3A, CD163, FCGR3B, and CCR2. This study shows that, in Luminal A early-stage BC, SLNs gene expression studies enable the identification of distinct immune profiles that may influence prognosis stratification and highlight key genes that could serve as potential targets for immunotherapy. [ABSTRACT FROM AUTHOR]