PT  - JOURNAL ARTICLE
AU  - Breanna M. Allen
AU  - Kamir J. Hiam
AU  - Cassandra E. Burnett
AU  - Anthony Venida
AU  - Rachel DeBarge
AU  - Yaron Carmi
AU  - Matthew H. Spitzer
TI  - The Development, Function, and Plasticity of the Immune Macroenvironment in Cancer
AID  - 10.1101/805473
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 805473
4099  - http://biorxiv.org/content/early/2019/10/16/805473.short
4100  - http://biorxiv.org/content/early/2019/10/16/805473.full
AB  - Harnessing immune defense mechanisms has revolutionized cancer therapy, but our understanding of the factors governing immune responses in cancer remains incomplete, limiting patient benefit. Here, we use mass cytometry to define the organism-wide immune landscape in response to tumor development across five tissues in eight tumor models. Systemic immunity was dramatically altered across mouse models and cancer patients, with changes in peripheral tissues differing from those in the tumor microenvironment and taking place in phases during tumor growth. This tumor-experienced immune system mounted dampened responses to orthogonal challenges, including reduced T cell activation during viral or bacterial infection. Disruptions in T cell responses were not cell-intrinsic but rather due to reduced responses in antigen-presenting cells (APCs). Promoting APC activation was sufficient to restore T cell responses to orthogonal infection. All systemic immune changes were reversed with surgical tumor resection, revealing remarkable plasticity in the systemic immune state, which contrasts with terminal immune dysfunction in the tumor microenvironment. These results demonstrate that tumor development dynamically reshapes the composition and function of the immune macroenvironment.