P-03.03 Granulopoiesis and thrombopoiesis aberrantly synergize in cancer to promote tumor progression
Year: 2025
Type: conference-abstract
Abstract: Background Myeloid cells acquire tumor-supporting properties in cancer. Clinical strategies targeting this pathological process, however, are not established since the underlying mechanisms remain ill-defined. This study aimed at investigating tumor-elicited effects on bone marrow thrombopoiesis and granulopoiesis, thus uncovering the occurence of an aberrant, pro-tumorigenic interplay of these fundamental biological processes in cancer. Materials and Methods In vitro assays and mass spectrometry-based proteomics along with advanced in vivo/ex vivo microscopy techniques were employed in mouse models of TNBC. Transcriptomic, flow cytometric, and immunohistochemical analyses were performed in human bone marrow, blood, and/or tumors in triple-negative breast cancer (TNBC) and other solid cancers to validate identified molecular targets. Results Bone marrow megakaryocytes adopt an anabolic-inflammatory state in TNBC, which attracts aged neutrophils having returned from the circulation. Subsequently, these neutrophils form extracellular traps, in which myeloperoxidase destabilizes megakaryocyte extensions (=proplatelets) through hypochlorous acid-dependent processes. This enables monocytes to shed proplatelets into the bloodstream, thus generating immature/reticulated platelets with highly immunomodulatory properties. Concomitantly, megakaryocyte interactions with neutrophils freshly produced by tumor-initiated granulopoiesis shift their phenotype pro-angiogenic, before these neutrophils leave the bone marrow. In the tumor, immature/reticulated platelets recruit pro-angiogenic neutrophils for aberrant vessel formation, collectively fueling malignant growth. Mechanistically, these events rely on excessive tumor-associated thrombopoietin production, which correlates with impaired survival in various solid cancers. Conclusions Our translational studies identify a self-supporting mechanism in solid malignancies that synergistically dysregulates bone marrow granulo- and thrombopoiesis. Interfering with this irregular interrelation of hemostasis and immune system might represent an innovative concept to counteract tumor progression in TNBC and other cancers. B. Smiljanov: None.
Source: Poster presentations
Author: B Smiljanov
Institutions: LMU Klinikum, Ludwig-Maximilians-Universität München
Language: English
Topic: Immune cells in cancer
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4408836473