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

Published: 12 May 2023| Version 1 | DOI: 10.17632/ctnpxxdgrt.1
Dimitris Stellas, Sevasti Karaliota, Vasiliki Stravokefalou, Matthew Angel, Bethany Nagy, Katherine Goldfarbmuren, Cristina Bergamaschi, Barbara Felber, George Pavlakis


Locoregional monotherapy with heterodimeric 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 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, has also 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.



National Cancer Institute


Breast Cancer




National Institutes of Health

Contract No. HHSN261201500003I

National Institutes of Health

Intramural Funding