Metastatic breast cancer (MBC) is generally considered incurable and is characterized by marked biological and clinical heterogeneity. This underscores the need for novel prognostic and predictive biomarkers to guide individualized treatment. Over the past decades, the importance of the immune system in cancer progression has become increasingly recognized. There is, however, its role in metastatic disease remains insufficiently understood, in part due to limited knowledge of the immune landscape in metastases. We have recently identified a panel of serum immune-oncology markers with strong prognostic value in MBC. Whether these markers are reflected in metastatic tissue, retain prognostic relevance at the tissue level, and what biological mechanisms underlie these associations remain unknown. In this study, we will apply single-cell spatial transcriptomics (Xenium In Situ) on breast cancer metastases and i) determine the tissue expression levels of the identified markers, ii) assess the correlation between tissue expression levels and serum levels, iii) evaluate their prognostic value when present in metastases and if such associations are found, iv) explore potential underlying mechanisms based on involved cell types expressing these markers and biological processes that are affected in these cells or adjacent cells. This study has potential to provide mechanistic insights into how circulating immune markers relate to the tumor microenvironment in MBC, potentially identifying biologically relevant pathways that could be therapeutically targeted.