Interferon-Induced Monocyte Immune Response Augments Immunotherapy and Correlates with Clinical Outcomes in Breast Cancer

Abstract

Abstract In this study, we established comprehensive single-cell transcriptomic profiles of myeloid cells and T cells in breast cancer and identified a group of monocytes that secrete various chemokines to promote anti-tumor immunity and respond to interferon-gamma (IFN-γ), as well as a group of T cells that self-secrete IFN-γ. Notably, these T cells not only serve as targets of IFN-γ but can also produce IFN-γ themselves. We observed a strong positive feedback loop between these unique monocytes and T cells. The monocytes secrete various chemokines to recruit T cells into the tumor microenvironment. Additionally, they produce SPP1, stimulating DC cells to produce IL-12, which further promotes the production of IFN-γ by T cells. On the other hand, the IFN-γ secreted by T cells further activates monocytes. Furthermore, after immunotherapy, there was a significant increase in these unique monocytes in the tumor microenvironment, indicating that they could serve as biomarkers of immunotherapeutic response and possess the potential to activate anti-tumor immunity. Finally, survival analysis and immune fluorescence staining of patient samples support the correlation between the density of these unique monocytes and patient prognosis. These findings underscore the importance of monocytes and their interactions with T cells in breast cancer, providing insights into potential targets for immunotherapy and prognosis assessment.