CD301b+ monocyte-derived dendritic cells mediate resistance to radiotherapy
Monocytes infiltrating tumors acquire various states that distinctly impact cancer treatment. Here, we show that resistance of tumors to radiotherapy (RT) is controlled by the accumulation of monocyte-derived dendritic cells (moDCs). These moDCs are characterized by the expression of CD301b and have a superior capacity to generate regulatory T cells (Tregs). Accordingly, moDC depletion limits Treg generation and improves the therapeutic outcome of RT. Mechanistically, we demonstrate that granulocyte-macrophage colony-stimulating factor (GM-CSF) derived from radioresistant tumor cells following RT is necessary for the accumulation of moDCs. Our results unravel the immunosuppressive function of moDCs and identify GM-CSF as an immunotherapeutic target during RT.
Authors
- David Seong (ORCID: https://orcid.org/0000-0002-8980-5731)
- Andres Gottfried‐Blackmore (ORCID: https://orcid.org/0000-0002-3563-3727)
- Anja Lüdtke
- Jan E. Carette (ORCID: https://orcid.org/0000-0002-5187-8070)
- Sirimuvva Tadepalli (ORCID: https://orcid.org/0000-0001-9658-9988)
- Juliana Idoyaga (ORCID: https://orcid.org/0000-0002-4430-8862)
- Sanjana Saravanan (ORCID: https://orcid.org/0000-0002-5974-7710)
- Hayley M. Raquer-McKay (ORCID: https://orcid.org/0000-0002-7404-8221)
- Matthias Mack (ORCID: https://orcid.org/0000-0002-3157-7262)
- Derek R. Clements (ORCID: https://orcid.org/0000-0002-0796-8845)
- Edward E. Graves (ORCID: https://orcid.org/0000-0003-4265-9041)
- Christopher M. Richards (ORCID: https://orcid.org/0000-0003-0832-8951)
- Lorraine Vitek
Institutions
- University Hospital Regensburg (DE)
- University of California San Diego (US)
- VA San Diego Healthcare System (US)
- Stanford University (US)
Publication Details
- Journal
- The Journal of Experimental Medicine
- Published
- 2025-03-27
- DOI
- https://doi.org/10.1084/jem.20231717
- Citations
- 9
- Primary Topic
- Immunotherapy and Immune Responses
- Type
- article
- Field-Weighted Citation Impact
- 7.18
Funders
- National Science Foundation
- Stanford University
- Life Sciences Research Foundation
- National Institutes of Health
- School of Medicine, Stanford University
- Canadian Institutes of Health Research