Zdroj: |
Lende, S S F, Pahus, M H, Monrad, I, Olesen, R, Mahr, A R, Vibholm, L K, Østergaard, L, Søgaard, O S, Andersen, A H F, Denton, P W & Tolstrup, M 2022, ' CD169 (Siglec-1) as a Robust Human Cell Biomarker of Toll-Like Receptor 9 Agonist Immunotherapy ', Frontiers in cellular and infection microbiology, vol. 12, 919097 . https://doi.org/10.3389/fcimb.2022.919097 |
Popis: |
Immunotherapy is a promising therapeutic area in cancer and chronic viral infections. An important component of immunotherapy in these contexts is the activation of innate immunity. Here we investigate the potential for CD169 (Siglec 1) expression on monocytes to serve as a robust biomarker for activation of innate immunity and, particular, as a proxy for IFN-α production. Specifically, we investigated the effects of Toll-like receptor 9 agonism with MGN1703 (lefitolimod) across experimental conditions ex vivo, in humanized mice, and in clinical trial participants. Ex vivo we observed that the percentage of classical monocytes expressing CD169 increased dramatically from 10% pre-stimulation to 97% 24 hrs after MGN1703 stimulation (pex vivo, in an animal model, and in a clinical trial, we find increases in the percentage of CD169 positive monocytes to be a reliable and robust biomarker of immune activation following TLR9 agonist treatment. |