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Open AccessArticle

STAT3 Inhibits CD103+ cDC1 Vaccine Efficacy in Murine Breast Cancer

Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
MD Anderson UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA
Author to whom correspondence should be addressed.
Cancers 2020, 12(1), 128;
Received: 26 November 2019 / Revised: 30 December 2019 / Accepted: 2 January 2020 / Published: 4 January 2020
(This article belongs to the Special Issue JAK-STAT Signalling Pathway in Cancer)
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-γ+ 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. View Full-Text
Keywords: CD103+ dendritic cells; cDC1; STAT3; breast cancer; immunotherapy; tumor vaccine; immunosuppression CD103+ dendritic cells; cDC1; STAT3; breast cancer; immunotherapy; tumor vaccine; immunosuppression
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Chrisikos, T.T.; Zhou, Y.; Li, H.S.; Babcock, R.L.; Wan, X.; Patel, B.; Newton, K.; Mancuso, J.J.; Watowich, S.S. STAT3 Inhibits CD103+ cDC1 Vaccine Efficacy in Murine Breast Cancer. Cancers 2020, 12, 128.

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