The consequences of progenitor neutrophil evacuation into the periphery during breast cancer

Recent results suggest neutrophil progenitors and immature neutrophils are appearing in the periphery in response to cancer and pathogens. The tumor microenvironment (TME) may take advantage of neutrophil progenitor susceptibility by signaling for the neutrophil to support tumor growth. This project tests the hypothesis that neutrophil progenitors experiencing the periphery during cancer will take on unique phenotypic and functional states depending on which tissue they are transferred into, and to which tissues they transit to post-transfer. In mice bearing PyMT B6 orthotopic tumors, congenically marked CD45.2 + neutrophil progenitors were transferred into CD45.1 + recipient mice. Two neutrophil progenitor populations were transferred: total bone marrow neutrophils (Ly6G + ), and pre-neus (CD117 + Ly6G + ). Cells were transferred into the blood of tumor and non-tumor bearing mice, and into the tumor of tumor bearing mice. After 1 day, tissues were isolated to quantitate adoptively transferred cells in the following tissues: bone marrow, blood, spleen, tumor and lymph nodes. Adoptively transferred cells were also measured for changes in phenotype using spectral flow cytometry and changes in function, including their ability to produce Reactive Oxygen Species (ROS), an anti-microbial function of neutrophils. Preliminary results show that the site of adoptive transfer affects the accumulation of adoptively transferred cells in tissues. Together, these data will help us further understand how tissue environments directly shape neutrophil phenotype and function. If we identify tissue environments influencing neutrophil functionality and expression, especially if promoting pro-tumoral functions, we can further identify pathways and signals to block therapeutically. This method may depress tumor progression, increasing patient survival rates.