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

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 metas-tasis, 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 corre-late with tumor regression. Therefore, hetIL-15, a cytokine directly affecting lymphocytes and inducing cyto-toxic 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 can-cer immunotherapy approaches.

Automated summary

In a triple-negative breast cancer (TNBC) orthotopic mouse model, locoregional monotherapy with heterodimeric interleukin (IL)-15 (hetIL-15) led to tumor eradication in 40% of treated mice, reduction of metastasis, and development of immunological memory. hetIL-15 reshaped the tumor microenvironment by promoting the accumulation of cytotoxic lymphocytes, conventional type 1 dendritic cells (cDC1s), and a dendritic cell (DC) population expressing both CD103 and CD11b markers. The hetIL-15-induced CD103intCD11b+ DC population has characteristics resembling both cDC1s and cDC2s, and is associated with tumor regression.