2. Academic Validation
  3. Systemic dysfunction and plasticity of the immune macroenvironment in cancer models

Systemic dysfunction and plasticity of the immune macroenvironment in cancer models

  • Nat Med. 2020 Jul;26(7):1125-1134. doi: 10.1038/s41591-020-0892-6.
Breanna M Allen # 1 2,  Kamir J Hiam # 1 2,  Cassandra E Burnett 1 2,  Anthony Venida 1 3,  Rachel DeBarge 1 2,  Iliana Tenvooren 2,  Diana M Marquez 2,  Nam Woo Cho 2 4,  Yaron Carmi 5,  Matthew H Spitzer 6 7
Affiliations

Affiliations

  • 1 Graduate Program in Biomedical Sciences, University of California, San Francisco, San Francisco, CA, USA.
  • 2 Departments of Otolaryngology and Microbiology & Immunology, Helen Diller Family Comprehensive Cancer Center, Parker Institute for Cancer Immunotherapy, Chan Zuckerberg Biohub, University of California, San Francisco, San Francisco, CA, USA.
  • 3 Department of Anatomy, University of California San Francisco, San Francisco, CA, USA.
  • 4 Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
  • 5 Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • 6 Graduate Program in Biomedical Sciences, University of California, San Francisco, San Francisco, CA, USA. matthew.spitzer@ucsf.edu.
  • 7 Departments of Otolaryngology and Microbiology & Immunology, Helen Diller Family Comprehensive Cancer Center, Parker Institute for Cancer Immunotherapy, Chan Zuckerberg Biohub, University of California, San Francisco, San Francisco, CA, USA. matthew.spitzer@ucsf.edu.
  • # Contributed equally.
PMID: 32451499 DOI: 10.1038/s41591-020-0892-6
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.

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