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Updated: May 20, 2025
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Isolation Protocol of Mouse Monocyte-derived Dendritic Cells and Their Subsequent In Vitro Activation with Tumor Immune Complexes
Published on: May 31, 2018
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CD301b+ monocyte-derived dendritic cells mediate resistance to radiotherapy
Sirimuvva Tadepalli1,2,3, Derek R Clements1,2, Hayley M Raquer-McKay1,2
1Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
The Journal of Experimental Medicine
|March 27, 2025
Summary
Tumor resistance to radiotherapy (RT) is linked to immunosuppressive monocyte-derived dendritic cells (moDCs). Depleting these cells and targeting granulocyte-macrophage colony-stimulating factor (GM-CSF) can improve RT outcomes.
Area of Science:
- Immunology
- Cancer Biology
- Radiotherapy Research
Background:
- Tumor-infiltrating monocytes adopt diverse phenotypes impacting cancer treatment efficacy.
- Tumor resistance to radiotherapy (RT) is a significant clinical challenge.
- Understanding the role of specific immune cells in RT resistance is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To investigate the role of monocyte-derived dendritic cells (moDCs) in tumor resistance to radiotherapy (RT).
- To elucidate the mechanisms by which moDCs contribute to an immunosuppressive tumor microenvironment during RT.
- To identify potential therapeutic targets for overcoming RT resistance.
Main Methods:
- Flow cytometry and immunohistochemistry to characterize tumor-infiltrating monocytes and moDCs.
- Depletion strategies targeting moDCs in preclinical tumor models.
- Analysis of regulatory T cell (Treg) generation in response to moDCs.
- Investigating the role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in moDC accumulation.
Main Results:
- Tumor resistance to RT correlates with the accumulation of CD301b-expressing moDCs.
- These moDCs exhibit a potent capacity to generate regulatory T cells (Tregs).
- Depletion of moDCs significantly limits Treg generation and enhances the therapeutic efficacy of RT.
- Granulocyte-macrophage colony-stimulating factor (GM-CSF) secreted by radioresistant tumor cells drives moDC accumulation.
Conclusions:
- Monocyte-derived dendritic cells (moDCs) play a critical immunosuppressive role in mediating tumor resistance to radiotherapy (RT).
- Targeting moDC accumulation, potentially by inhibiting GM-CSF, represents a promising immunotherapeutic strategy to improve RT outcomes.
- These findings highlight GM-CSF as a key target for enhancing cancer treatment with radiotherapy.
