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Tumor-associated neutrophils drive pre-metastatic immunosuppressive bone marrow remodeling in prostate cancer, emerging at the high-risk bone metastatic potential stage and correlating with poor patient prognosis. Tumor-associated systemic IGF1 reprograms marrow neutrophils via IGF1R-MAPK/ERK-KLF4 signaling, and Igf1 perturbation, IGF1R blockade or neutrophil-specific Igf1r deletion reduces bone metastatic progression. An investigator-initiated trial of teprotumumab plus tislelizumab in metastatic castration-resistant prostate cancer provided initial safety data.
Excerpted from biorxiv.org
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- biorxiv.orgNeutrophils orchestrate pre-metastatic immunosuppressive bone marrow remodeling during prostate cancer metastasis
Tumor-associated neutrophils drive pre-metastatic immunosuppressive bone marrow remodeling in prostate cancer, emerging at the high-risk bone metastatic potential stage and correlating with poor patient prognosis. Tumor-associated systemic IGF1 reprograms marrow neutrophils via IGF1R-MAPK/ERK-KLF4 signaling, and Igf1 perturbation, IGF1R blockade or neutrophil-specific Igf1r deletion reduces bone metastatic progression. An investigator-initiated trial of teprotumumab plus tislelizumab in metastatic castration-resistant prostate cancer provided initial safety data.
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