Tumor-Mediated Neutrophil Polarization and Therapeutic Implications

Neutrophils are immune cells with reported phenotypic and functional plasticity. Tumor-associated neutrophils display many roles during cancer progression. Several tumor microenvironment (TME)-derived factors orchestrate neutrophil release from the bone marrow, recruitment and functional polarization, while simultaneously neutrophils are active stimulators of the TME by secreting factors that affect immune interactions and subsequently tumor progression. Successful immunotherapies for many cancer types and stages depend on the targeting of tumor-infiltrating lymphocytes. Neutrophils impact the success of immunotherapies, such as immune checkpoint blockade therapies, by displaying lymphocyte suppressive properties. The identification and characterization of distinct neutrophil subpopulations or polarization states with pro- and antitumor phenotypes and the identification of the major TME-derived factors of neutrophil polarization would allow us to harness the full potential of neutrophils as complementary targets in anticancer precision therapies

The human placenta shapes the phenotype of decidual macrophages

During human pregnancy, placenta-derived extravillous trophoblasts (EVTs) invade the decidua and commu-nicate with maternal immune cells. The decidua distinguishes into basalis (decB) and parietalis (decP). The latter remains unaffected by EVT invasion. By defining a specific gating strategy, we report the accumulation of macrophages in decB. We describe a decidua basalis-associated macrophage (decBAM) population with a differential transcriptome and secretome compared with decidua parietalis-associated macrophages (dec-PAMs). decBAMs are CD11chi and efficient inducers of Tregs, proliferate in situ, and secrete high levels of CXCL1, CXCL5, M-CSF, and IL-10. In contrast, decPAMs exert a dendritic cell-like, motile phenotype char-acterized by induced expression of HLA class II molecules, enhanced phagocytosis, and the ability to acti-vate T cells. Strikingly, EVT-conditioned media convert decPAMs into a decBAM phenotype. These findings assign distinct macrophage phenotypes to decidual areas depending on placentation and further highlight a critical role for EVTs in the induction of decB-associated macrophage polarization.Funding Agencies|Clinical biomarker facility at SciLifeLab Sweden; Austrian Science Fund [P33485]; Austrian National Bank [17613ONB]</p