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Tumor eradication by hetIL-15 locoregional therapy correlates with an induced intratumoral CD103intCD11b+ dendritic cell population

  1. Author:
    Stellas, Dimitris
    Karaliota,Sevasti
    Stravokefalou, Vasiliki
    Angel, Matthew
    Nagy,Bethany
    Goldfarbmuren,Kate
    Bergamaschi, Cristina
    Felber,Barbara
    Pavlakis,George

  2. Author Address

    Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA; Department of Chemical Biology, National Hellenic Research Foundation, 11635 Athens, Greece. Electronic address: george.pavlakis@nih.gov., Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA; Basic Science Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21702, USA., Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA; Department of Pharmacology, Faculty of Medicine, University of Thessaly, 41500 Larissa, Greece., Vaccine Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21702, USA., Laboratory Animal Sciences Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21702, USA., Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA., Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA. Electronic address: george.pavlakis@nih.gov.,
    1. Year: 2023
    2. Date: May 12
    3. Epub Date: 2023 05 12
  2. Journal: Cell Reports
    1. 42
    2. 5
    3. Pages: 112501
  4. Type of Article: Article
  5. Article Number: 112501
  1. Abstract:

    Locoregional monotherapy with heterodimeric interleukin (IL)-15 (hetIL-15) in a triple-negative breast cancer (TNBC) orthotopic mouse model resulted in tumor eradication in 40% of treated mice, reduction of metastasis, and induction of immunological memory against breast cancer cells. hetIL-15 re-shaped the tumor microenvironment by promoting the intratumoral accumulation of cytotoxic lymphocytes, conventional type 1 dendritic cells (cDC1s), and a dendritic cell (DC) population expressing both CD103 and CD11b markers. These CD103intCD11b+DCs share phenotypic and gene expression characteristics with both cDC1s and cDC2s, have transcriptomic profiles more similar to monocyte-derived DCs (moDCs), and correlate with tumor regression. Therefore, hetIL-15, a cytokine directly affecting lymphocytes and inducing cytotoxic cells, also has an indirect rapid and significant effect on the recruitment of myeloid cells, initiating a cascade for tumor elimination through innate and adoptive immune mechanisms. The intratumoral CD103intCD11b+DC population induced by hetIL-15 may be targeted for the development of additional cancer immunotherapy approaches. Published by Elsevier Inc.

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External Sources

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  2. DOI: 10.1016/j.celrep.2023.112501
  3. PMID: 37178117
  4. PII : S2211-1247(23)00512-0

Library Notes

  1. Fiscal Year: FY2022-2023
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