Multimodal imaging of the tumor microenvironment and biological responses to immune therapy

Alexander M. Saucedo, Jorge De La Cerda, Hiroo Suami, Rita E. Serda

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Beyond heterogeneous cancer cells, the tumor microenvironment includes stromal and immune cells, blood vessels, extracellular matrix and biologically active molecules. Abnormal signaling, uncontrolled proliferation and high interstitial pressure all contribute to a chaotic, non-hierarchical vascular organization. Using an immune competent 4T1 breast adenocarcinoma murine model, this study fully characterizes the architecture and immunocyte milieu of the tumor microenvironment. Heterogeneous vessel distribution, chaotic connectivity, limited perfusion, cancer cell density, immune phenotype, and biological responses to immune therapy are presented. Cancer cell density mirrored the distribution of large, perfusable vessels, both predominately in the tumor periphery. Intratumoral administration of the proinflammatory cytokine IL-12 led to an increase in CD45+ leukocytes, with a specific increase in CD4+ and CD8+ T cells, and a decrease in the percentage of Gr-llo myeloid-derived suppressor cells. Concomitantly, serum G-CSF, IL-10 and VEGF decreased, while CXCR9 and interferon gamma increased. The distribution pattern of infiltrating monocytes/macrophages, visualized using a fluorescent perfluorocarbon emulsion, indicated that macrophages predominately localize in the vicinity of large blood vessels. Electron microscopy supports the presence of dense tumor cell masses throughout the tumor, with the largest vessels present in the surrounding mammary fat pad. Overall, large vessels in the 4T1 tumor periphery support high, localized vascular perfusion and myeloid accumulation. The pro-inflammatory cytokine IL-12 stimulated a transition towards T helper 1 cytokines in serum, supporting suppression of tumor growth and angiostatic conditions.

LanguageEnglish
Article number105
Pages1-10
Number of pages10
JournalBiomedical Microdevices
Volume20
Issue number4
Early online date3 Dec 2018
DOIs
Publication statusPublished - 2018

Fingerprint

Multimodal Imaging
Tumor Microenvironment
Tumors
Imaging techniques
Blood Vessels
Cells
Neoplasms
Macrophages
Blood vessels
Therapeutics
Interleukin-12
Cytokines
Breast
Interferons
Perfusion
Cell Count
T-cells
Cellular Microenvironment
Fluorocarbons
Oils and fats

Keywords

  • computed tomography
  • Electron microscopy
  • Interleukin 12
  • Magnetic resonance imaging
  • Tumor vasculature

Cite this

Saucedo, Alexander M. ; De La Cerda, Jorge ; Suami, Hiroo ; Serda, Rita E. / Multimodal imaging of the tumor microenvironment and biological responses to immune therapy. In: Biomedical Microdevices. 2018 ; Vol. 20, No. 4. pp. 1-10.
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Multimodal imaging of the tumor microenvironment and biological responses to immune therapy. / Saucedo, Alexander M.; De La Cerda, Jorge; Suami, Hiroo; Serda, Rita E.

In: Biomedical Microdevices, Vol. 20, No. 4, 105, 2018, p. 1-10.

Research output: Contribution to journalArticleResearchpeer-review

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