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.
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.
Cell Rep. 2023 May 30;42(5):112501. doi: 10.1016/j.celrep.2023.112501. Epub 2023 May 12.
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 CD103CD11bDCs 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 CD103CD11bDC population induced by hetIL-15 may be targeted for the development of additional cancer immunotherapy approaches.
局部区域单药治疗三阴性乳腺癌（TNBC）的异二聚体白细胞介素（IL）-15（hetIL-15）在 40%的治疗小鼠中导致肿瘤消除，减少转移，并诱导针对乳腺癌细胞的免疫记忆。hetIL-15 通过促进肿瘤内细胞毒性淋巴细胞、传统 1 型树突状细胞（cDC1）和表达 CD103 和 CD11b 标志物的树突状细胞（DC）群体的积累，重塑肿瘤微环境。这些 CD103CD11bDC 具有与 cDC1 和 cDC2 相似的表型和基因表达特征，转录组谱与单核细胞衍生的 DC（moDC）更相似，与肿瘤消退相关。因此，hetIL-15 作为一种直接影响淋巴细胞并诱导细胞毒性细胞的细胞因子，也对髓样细胞的募集产生快速而显著的间接影响，通过先天和适应性免疫机制引发肿瘤消除级联反应。hetIL-15 诱导的肿瘤内 CD103CD11bDC 群体可能成为开发其他癌症免疫治疗方法的目标。
