| First Author | Rucker AJ | Year | 2024 |
| Journal | Cell Death Dis | Volume | 15 |
| Issue | 6 | Pages | 403 |
| PubMed ID | 38858387 | Mgi Jnum | J:354558 |
| Mgi Id | MGI:7658043 | Doi | 10.1038/s41419-024-06801-8 |
| Citation | Rucker AJ, et al. (2024) Necroptosis stimulates interferon-mediated protective anti-tumor immunity. Cell Death Dis 15(6):403 |
| abstractText | Necroptosis is an inflammatory form of cell suicide that critically depends on the kinase activity of Receptor Interacting Protein Kinase 3 (RIPK3). Previous studies showed that immunization with necroptotic cells conferred protection against subsequent tumor challenge. Since RIPK3 can also promote apoptosis and NF-kappaB-dependent inflammation, it remains difficult to determine the contribution of necroptosis-associated release of damage-associated molecular patterns (DAMPs) in anti-tumor immunity. Here, we describe a system that allows us to selectively induce RIPK3-dependent necroptosis or apoptosis with minimal NF-kappaB-dependent inflammatory cytokine expression. In a syngeneic tumor challenge model, immunization with necroptotic cells conferred superior protection against subsequent tumor challenge. Surprisingly, this protective effect required CD4(+) T cells rather than CD8(+) T cells and is dependent on host type I interferon signaling. Our results provide evidence that death-dependent type I interferon production following necroptosis is sufficient to elicit protective anti-tumor immunity. |
