Multi-organ transcriptomic and functional characterization of tumor-associated neutrophils in breast cancer 4374

Description Neutrophil accumulation is associated with worse prognosis and immunotherapy resistance in many cancer types. Tumor-associated neutrophils (TANs) emerge systemically in the tumor-bearing host, and have been shown to promote tumor progression and metastasis through suppression of the anti-tumor immune response. However, it is unclear how neutrophil progenitors develop into TANs and if there are targetable markers differentiating normal neutrophils and TANs. Here, we performed single-cell RNA sequencing on neutrophils from bone marrow, spleen, lymph nodes, blood, mammary gland, tumor, and lungs from wild-type and breast tumor-bearing MMTV-PyMT mice. We describe five transcriptional states, N0-N4, which encompass normal neutrophil maturation, as well as a sixth state composed of TANs. From this dataset, we identified novel differentially expressed genes including IL-1R2 on mature mammary gland neutrophils, and IFITM1 and AMWAP on MMTV-PyMT TANs. IFITM1+ neutrophils were found to be expanded in tumor-bearing mice and suppressed T cell proliferation and activation compared to their wild-type counterparts. Taken altogether, this work provides a systemic, multi-organ perspective into TAN development and identifies TAN-specific markers which may be potential targets to inhibit cancer-induced immunosuppression. Funding Sources NIH T32CA009054 Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)