Systemic dysfunction and plasticity of the immune macroenvironment in cancer models

Breanna M. Allen, Kamir J. Hiam, Cassandra E. Burnett, Anthony Venida, Rachel DeBarge, Iliana Tenvooren, Diana M. Marquez, Nam Woo Cho, Yaron Carmi, Matthew H. Spitzer

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1125-1134
Number of pages10
JournalNature Medicine
Volume26
Issue number7
DOIs
StatePublished - 1 Jul 2020

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