@article{17adbf2b66984f719b4e7b568fc3f0d4,
title = "Systemic dysfunction and plasticity of the immune macroenvironment in cancer models",
abstract = "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.",
author = "Allen, {Breanna M.} and Hiam, {Kamir J.} and Burnett, {Cassandra E.} and Anthony Venida and Rachel DeBarge and Iliana Tenvooren and Marquez, {Diana M.} and Cho, {Nam Woo} and Yaron Carmi and Spitzer, {Matthew H.}",
note = "Funding Information: We thank the UCSF Flow Cytometry Core and S. Tamaki for CyTOF maintenance and M.H. Barcellos-Hoff, R. Levine, H. Okada, E. Engleman and J. Bluestone for cell lines, transgenic mice and reagents. We thank L. Lanier, Z. Werb, M.H. Barcellos-Hoff and L. Fong for insightful feedback. This work was supported by National Institutes of Health (NIH) grants DP5OD023056 and P50CA097257 (UCSF Brain Tumor SPORE Developmental Research Program), funds from the UCSF Program for Breakthrough Biomedical Research and investigator funding from the Parker Institute for Cancer Immunotherapy to M.H.S. and by NIH grant S10OD018040, which enabled procurement of the mass cytometer used in this study. This study makes use of data generated by the Norwegian Women and Cancer Study. A full list of investigators who contributed to the generation of the data is available at http://site.uit.no/nowac/. Funding for the project was provided by European Research Council grant ERC-2008-AdG 232997. The Norwegian Women and Cancer Study group is not responsible for the analysis or interpretation of the data presented. Funding Information: M.H.S. receives research funding from Roche/Genentech, Bristol-Myers Squibb and Valitor and has been a paid consultant for Five Prime Therapeutics, Ono Pharmaceutical and January Inc. Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2020",
month = jul,
day = "1",
doi = "10.1038/s41591-020-0892-6",
language = "English",
volume = "26",
pages = "1125--1134",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "7",
}
