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Related Experiment Video

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Profiling specific cell populations within the inflammatory tumor microenvironment by oscillating-gradient

Emily Hoffmann1, Mirjam Gerwing1, Stephan Niland2

  • 1Clinic of Radiology, University of Münster, Münster, Germany.

Journal for Immunotherapy of Cancer
|March 14, 2023
PubMed
Summary

Oscillating-gradient diffusion-weighted MRI (OGSE-DWI) can differentiate between T-cells and macrophages in the tumor microenvironment (TME). This imaging technique offers a non-invasive method to assess immune cell populations, aiding in understanding tumor progression and treatment response.

Keywords:
T-lymphocytesimmunotherapymacrophagestranslational medical researchtumor microenvironment

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Area of Science:

  • Oncology
  • Immunology
  • Medical Imaging

Background:

  • The inflammatory tumor microenvironment (TME) is crucial in tumorigenesis, with T-cell and macrophage interactions significantly impacting tumor progression.
  • Understanding the composition of the TME is vital for developing effective cancer therapies.

Purpose of the Study:

  • To investigate the utility of oscillating-gradient diffusion-weighted MRI (OGSE-DWI) for non-invasively discriminating between different immune cell populations within the TME based on cell size.
  • To assess the potential of OGSE-DWI in monitoring changes in TME composition during tumor progression and therapeutic interventions.

Main Methods:

  • Combined sine-shaped OGSE-DWI with the Imaging Microstructural Parameters Using Limited Spectrally Edited Diffusion (IMPULSED) approach to measure microscale diffusion distances related to cell sizes.
  • Validated IMPULSED-derived cell radii using in vitro spheroid models of cancer cells, macrophages, and T-cells.
  • Conducted in vivo experiments in murine breast cancer models, including assessments during tumor progression, macrophage depletion, and immune checkpoint inhibitor (ICI) treatment, with ex vivo validation via immunohistochemistry.

Main Results:

  • OGSE-DWI successfully differentiated cell populations, measuring distinct mean cell radii for cancer cells, macrophages, and T-cells.
  • Observed changes in mean cell radii correlated with T-cell infiltration and macrophage accumulation during tumor progression in different murine models.
  • Demonstrated that OGSE-DWI could detect alterations in TME composition following macrophage depletion and ICI treatment, reflecting changes in immune cell populations.

Conclusions:

  • OGSE-DWI, coupled with IMPULSED, is a powerful non-invasive tool for profiling the inflammatory TME.
  • This technique enables cell size-based discrimination of dominant immune cell types, specifically T-cells and macrophages.
  • OGSE-DWI holds significant potential for monitoring therapeutic responses and understanding immune dynamics in cancer.