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Publication : Systemic dysfunction and plasticity of the immune macroenvironment in cancer models.

First Author  Allen BM Year  2020
Journal  Nat Med Volume  26
Issue  7 Pages  1125-1134
PubMed ID  32451499 Mgi Jnum  J:306049
Mgi Id  MGI:6710321 Doi  10.1038/s41591-020-0892-6
Citation  Allen BM, et al. (2020) Systemic dysfunction and plasticity of the immune macroenvironment in cancer models. Nat Med 26(7):1125-1134
abstractText  Understanding of the factors governing immune responses in cancer remains incomplete, limiting patient benefit. In this study, we used mass cytometry to define the systemic immune landscape in response to tumor development across five tissues in eight mouse tumor models. Systemic immunity was dramatically altered across models and time, with consistent findings in the peripheral blood of patients with breast cancer. Changes in peripheral tissues differed from those in the tumor microenvironment. Mice with tumor-experienced immune systems mounted dampened responses to orthogonal challenges, including reduced T cell activation during viral or bacterial infection. Antigen-presenting cells (APCs) mounted weaker responses in this context, whereas promoting APC activation rescued T cell activity. Systemic immune changes were reversed with surgical tumor resection, and many were prevented by interleukin-1 or granulocyte colony-stimulating factor blockade, revealing remarkable plasticity in the systemic immune state. These results demonstrate that tumor development dynamically reshapes the composition and function of the immune macroenvironment.
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