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Interleukin-2 signals converge in a lymphoid–dendritic cell pathway that promotes anticancer immunity.
- Source :
- Science Translational Medicine; 9/16/2020, Vol. 12 Issue 561, p1-16, 16p
- Publication Year :
- 2020
-
Abstract
- Hidden virtues of interleukin-2: Interleukin-2 (IL-2) is an immunostimulatory cytokine that is being tested as an anticancer therapy due to its ability to activate T cells and natural killer cells. Unexpectedly, Raeber et al. discovered that IL-2 can also activate dendritic cells, an entirely different type of cells involved in antitumor immunity. The authors analyzed data from a clinical trial in human patients being treated with recombinant IL-2. They also pursued more detailed studies in mouse models to identify the mechanisms responsible for dendritic cell activation, helping to explain how IL-2 sensitizes tumors to immune destruction. Tumor-infiltrating dendritic cells (DCs) correlate with effective anticancer immunity and improved responsiveness to anti–PD-1 checkpoint immunotherapy. However, the drivers of DC expansion and intratumoral accumulation are ill-defined. We found that interleukin-2 (IL-2) stimulated DC formation through innate and adaptive lymphoid cells in mice and humans, and this increase in DCs improved anticancer immunity. Administration of IL-2 to humans within a clinical trial and of IL-2 receptor (IL-2R)–biased IL-2 to mice resulted in pronounced expansion of type 1 DCs, including migratory and cross-presenting subsets, and type 2 DCs, although neither DC precursors nor mature DCs had functional IL-2Rs. In mechanistic studies, IL-2 signals stimulated innate lymphoid cells, natural killer cells, and T cells to synthesize the cytokines FLT3L, CSF-2, and TNF. These cytokines redundantly caused DC expansion and activation, which resulted in improved antigen processing and correlated with favorable anticancer responses in mice and patients. Thus, IL-2 immunotherapy–mediated stimulation of DCs contributes to anticancer immunity by rendering tumors more immunogenic. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 19466234
- Volume :
- 12
- Issue :
- 561
- Database :
- Complementary Index
- Journal :
- Science Translational Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 145734230
- Full Text :
- https://doi.org/10.1126/scitranslmed.aba5464