Spatial Single-Cell Transcriptomic Analysis in Breast Cancer Reveals Potential Biomarkers for PD1 Blockade Therapy

Understanding cellular crosstalk in the complex tumor microenvironment (TME) is crucial for unraveling the molecular mechanisms behind disease progression and response to therapies. Recent technological advancements enable spatial single-cell transcriptomic analysis of the TME; however, spatial transcriptomic data at true single-cell resolution are inadequate for dissecting the intricate architecture of the TME in breast and other cancers. The purpose of this study was to apply the latest spatial single-cell transcriptomics technology to dissect the breast cancer TME and identify potential biomarkers of therapeutic responses. We employed the cutting-edge Xenium technology to analyze the TME of various types of breast cancer including luminal-type, HER2+/HR-, and triple-negative breast cancer (TNBC). Our findings validated the effectiveness of the technology in achieving spatial cell annotation in the TME at the single-cell resolution. Notably, despite the diverse intrinsic features of various breast cancer types, spatial single-cell analysis of the TME revealed a prominent interplay among macrophages and T cells mediated by the CD274/CD80 interaction. This interplay aligns with the observed improvement in clinical responses to PD1 blockade therapies. Additionally, our results revealed that effector T cells, proliferative T cells, and macrophages localize closer to tumor cells in responders compared to non-responders of PD1 blockade therapy. Therefore, the CD274/CD80 ligand-receptor interaction, as well as the spatial localization of specific immune cells, represents potential biomarkers for future development for the advancement of immunotherapies in breast cancer.