Primary tumor hypoxia recruits CD11b/Ly6C/Ly6G immune suppressor cells and compromises NK cell cytotoxicity in the pre-metastatic niche
نویسندگان
چکیده
1 Cancer Genomics and Genetics Laboratory, 3 Cancer Immunology Program, and 6 Metastasis Research Group, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, Victoria 3002, Australia. 2 Department of Pathology, 5 Sir Peter MacCallum Department of Oncology, 7 Department of Biochemistry, The University of Melbourne, Parkville, Victoria 3010, Australia. 4 Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.
منابع مشابه
Primary tumor hypoxia recruits CD11b+/Ly6Cmed/Ly6G+ immune suppressor cells and compromises NK cell cytotoxicity in the premetastatic niche.
Hypoxia within a tumor acts as a strong selective pressure that promotes angiogenesis, invasion, and metastatic spread. In this study, we used immune competent bone marrow chimeric mice and syngeneic orthotopic mammary cancer models to show that hypoxia in the primary tumor promotes premetastatic niche formation in secondary organs. Injection of mice with cell-free conditioned medium derived fr...
متن کاملHypoxia-driven immunosuppression contributes to the pre-metastatic niche
Primary tumor cells create favorable microenvironments in secondary organs, termed pre-metastatic niches, that promote the formation of metastases. Using immune competent syngenic breast cancer mouse models, we have recently demonstrated that factors secreted by hypoxic tumor cells condition pre-metastatic niches by recruiting CD11b+/Ly6Cmed/Ly6G+ myeloid cells and suppressing natural killer ce...
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How myeloid-derived suppressor cells (MDSC) emerge in the tumor environment remains unclear. Here, we report that GM-CSF can convert natural killer (NK) cells into MDSCs. When transferred into tumor-bearing mice, adoptively transferred NK cells lost their NK phenotype and were converted into Ly6C(high)Ly6G(high) MDSC. This conversion was abolished by exposure to IL-2 either in vitro or in vivo....
متن کاملMicroenvironment and Immunology Primary Tumor Hypoxia Recruits CD11bþ/Ly6Cmed/Ly6Gþ Immune Suppressor Cells and Compromises NK Cell Cytotoxicity in the Premetastatic Niche
Hypoxia within a tumor acts as a strong selective pressure that promotes angiogenesis, invasion, and metastatic spread. In this study, we used immune competent bone marrow chimeric mice and syngeneic orthotopic mammary cancer models to show that hypoxia in the primary tumor promotes premetastatic niche formation in secondary organs. Injection of mice with cell-free conditioned medium derived fr...
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Myeloid-derived suppressor cells (MDSCs) are emerging as potential promoters of metastatic tumor growth, and there is interest in targeting immature MDSCs by inducing their differentiation into more mature myeloid cells. We used all-trans retinoic acid (ATRA) to differentiate MDSCs in mice bearing metastatic 4T1 or 4TO7 murine mammary tumors, and assessed the immune-suppressive mechanisms and p...
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