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MDSCs enhance tumor cell proliferation in a caspase-1 related inflammasome cytokines dependent way

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Myeloid-derived-suppression cells (MDSCs) are believed to be an important immune evasion mechanism by suppressing T cells. We investigated whether MDSCs have direct T cell independent pro-carcinogenic effect on tumor cells. We sorted the monocytic CD14+/CD11b+/HLA-DRlow MDSCs from head and neck squamous cell carcinoma (HNSCC) patients and found that MDSCs increased the proliferation index of HNSCC cells. Similar results were seen from co-culturing murine MDSCs and CT26 and B16 cells. Supernatant from the MDSCs were found to secrete inflammasome cytokines IL-1b and IL-18. MDSC's enhancement of proliferative index of the tumor was found to be caspase-1 dependent using FLICA. To test this in vivo, T cell depleted caspase-1 null mice showed significant decrease in tumor growth rate. To confirm the importance of myeloid inflammasome signaling in carcinogenesis, we suppressed MyD88 gene in tumor cell line Cal27 and found that the ability of MDSCs to promoting tumor proliferation is diminished. Taken together, our findings demonstrate that MDSCs can promote tumor cells proliferation on a inflammasome cytokines dependent manner.

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Correspondence to Qi Zeng.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Zeng, Q., Qualliotine, J., Blosser, R. et al. MDSCs enhance tumor cell proliferation in a caspase-1 related inflammasome cytokines dependent way. j. immunotherapy cancer 3, P317 (2015) doi:10.1186/2051-1426-3-S2-P317

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Keywords

  • Squamous Cell Carcinoma
  • Null Mouse
  • Tumor Cell Proliferation
  • Neck Squamous Cell Carcinoma
  • Tumor Proliferation