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Immunosuppressive neutrophils are identified as a specialized heterogeneous population in cancer patients that accelerate tumor progression. However, the developmental stage and the source of this population remain elusive. To address this issue, we unified three reported neutrophil nomenclatures and demonstrated that immature neutrophils predominate tumor tissues of patients. On the quest to identify the origin of immature neutrophils, we unexpectedly discovered that immature neutrophils collected from the bone marrow of healthy people and mice reconstituted with human immune cells (HIS mice) are naturally immunosuppressive and tumor-promoting, whereas the mouse counterpart is not. Single-cell comparison of immature neutrophils isolated from human tumors, human bone marrow and HIS mouse bone marrow samples reveal FCN1 as a common marker for this heterogeneous population. To further investigate the link between peripheral and bone marrow immature neutrophils, we created a novel immunodeficient strain, to overcome the poor human neutrophil engraftment in the periphery. HIS mice based on this strain manifest similar kinetics of immature neutrophil expansion as cancer patients both in the bone marrow and periphery after tumor cell inoculation. Finally, we proved that eliminating bone marrow immature neutrophils delays tumor growth in HIS mice. In summary, human immunosuppressive neutrophils are predominantly immature neutrophils and targeting this population in bone marrow may represent a novel strategy for cancer immunotherapy. Citation Format: Wei Liu, Keying Che, Chun Lu, Jia Wei, Yan Li. Identification of immunosuppressive and tumor-promoting neutrophils in human bone marrow and a novel mouse model that supports human neutrophil engraftment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2878. |
