| First Author | Chrisikos TT | Year | 2020 |
| Journal | Cancers (Basel) | Volume | 12 |
| Issue | 1 | PubMed ID | 31947933 |
| Mgi Jnum | J:337195 | Mgi Id | MGI:7494087 |
| Doi | 10.3390/cancers12010128 | Citation | Chrisikos TT, et al. (2020) STAT3 Inhibits CD103(+) cDC1 Vaccine Efficacy in Murine Breast Cancer. Cancers (Basel) 12(1) |
| abstractText | Conventional dendritic cells (cDCs) are a critical immune population, composed of multiple subsets, and responsible for controlling adaptive immunity and tolerance. Although migratory type 1 cDCs (CD103(+) cDC1s in mice) are necessary to mount CD8(+) T cell-mediated anti-tumor immunity, whether and how tumors modulate CD103(+) cDC1 function remain understudied. Signal Transducer and Activator of Transcription 3 (STAT3) mediates the intracellular signaling of tumor-associated immunosuppressive cytokines, such as interleukin (IL)-10; thus, we hypothesized that STAT3 restrained anti-tumor immune responses elicited by CD103(+) cDC1s. Herein, we show that in vitro-derived STAT3-deficient (Stat3(/)) CD103(+) cDC1s are refractory to the inhibitory effects of IL-10 on Toll-like receptor 3 (TLR3) agonist-induced maturation responses. In a tumor vaccination approach, we found Stat3(/) CD103(+) cDC1s restrained mammary gland tumor growth and increased mouse survival more effectively than STAT3-sufficient CD103(+) cDC1s. In addition, vaccination with Stat3(/) CD103(+) cDC1s elicited increased amounts of tumor antigen-specific CD8(+) T cells and IFN-gamma(+) CD4(+) T cells in tumors and tumor-draining lymph nodes versus phosphate-buffered saline (PBS)-treated animals. Furthermore, IL-10 receptor-deficient CD103(+) cDC1s controlled tumor growth to a similar degree as Stat3(/) CD103(+) cDC1s. Taken together, our data reveal an inhibitory role for STAT3 in CD103(+) cDC1 maturation and regulation of anti-tumor immunity. Our results also suggest IL-10 is a key factor eliciting immunosuppressive STAT3 signaling in CD103(+) cDC1s in breast cancer. Thus, inhibition of STAT3 in cDC1s may provide an important strategy to improve their efficacy in tumor vaccination approaches and cDC1-mediated control of anti-tumor immunity. |
