Interrogating the Impact of Bone Metastasis-associated Myelopoiesis Skewing in Tumor Progression 4801

Abstract Description The coincidence of the myeloid-biased myelopoiesis skewing and lymphopoiesis impairments in bone microenvironment may hold the keys for constituting “cold” immune landscape tumors and restraining the efficacy of current immunotherapies. How Bone Metastatic (BnMet) cancer cells interact with myelopoietic progenitors to hijack the niche factors in favor of colonization cancer cells is still unclear. From the established a BnMet prostate cancer (PCa) model, interestingly, we observed that myelopoietic progenitors and inflammatory/pro-angiogenetic macrophages highly positively correlated with bone marrow(BM)-infiltrating tumor cells. The late stage of tumor expansion status arrested the terminal differentiation of Ly6Chiintermediate progenitors and promoted vigorous myelopoiesis. We identified that Siglec-F could be expressed on particularly myelopoietic progenitors and BM Ly6Chi monocytes via analysis of scRNAseq and the membrane-bound protein expression. We characterized the transcriptomic profiles, cellularity and immune signature of multiple immune organs in the BM chimera, which developed with Siglec-F+ vs Siglec-F- and WT vs Siglec-FKO progenitors. Of the 39 BnMet PCa patients, high ST6GAL2 and ST3GAL4 expressions were associated with relapse in OS and RFS in the WCDT-MCRPC cohort. This study suggests that Siglec-F-sialoglycoprotein axis can be a glycoimmunotherapeutic strategy for reprogramming disease-associated myeloid cells and ameliorating disease progress. Funding Sources NHRI-EX112-11221BI NSTC-111-2628-B-001 -016 -MY3 NSTC-110-2320-B-001-011-MY3 Academia Sinica Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)