Project description:Cancer dysregulates intratumoral adaptive-innate immune cell crosstalk, however, it remains largely unknown how the systemic immune landscape is modified during breast cancer progression and whether prior chemotherapy treatment exerts persistent changes on circulating immune cells. Here, we comprehensively profiled the systemic immune landscape in patients with triple negative breast cancer (TNBC) at distinct disease stages, to understand how cancer progression and treatment history shape the systemic immune landscape. We performed multi-parameter flow cytometry analysis to assess the global systemic immune landscape, including often overlooked granulocytes. We showed that patients with metastatic TNBC (mTNBC) exhibited increased classical monocytes and neutrophils compared to healthy donors (HDs) irrespective of prior therapy. Conversely, circulating T cells, dendritic cell subsets and differentiated B cells were reduced in patients with mTNBC compared to HDs, which could partially be attributed to prior chemotherapy treatment. Phenotypic and functional characterization of the T cell compartment revealed increased IL17 production by vδ1 γδ T cells, were increased. Transcriptional and proteomic analysis, alongside ex vivo functionality assays, revealed increased migratory capacity, increased granule proteins, and elevated ROS production in circulating neutrophils of mTNBC patients. Our data demonstrate that patient neutrophils are not only more abundant, but also display an altered functionality, underscoring the significant impact of TNBC disease stage and treatment history on the systemic immune composition and function.
