China Medical University (Taiwan)

Researchers have developed a web-based platform that offers an unprecedented view of the human body at the cellular level. The aim is to create an invaluable resource for researchers worldwide to increase knowledge about human health and disease. Researchers at Karolinska Institutet have developed a web-based platform that offers an unprecedented view of the human body at the cellular level. The aim is to create an invaluable resource for researchers worldwide to increase knowledge about human health and disease. The study is published in Genome Biology. Simultaneous measurement of numerous biomolecular variables, known as multi-omics, enables deep and comprehensive profiling of human biology. The new Single Cell Atlas (SCA) is based on analyses of thousands of human tissue samples from 125 different adult and fetal tissues. The researchers combined eight cutting-edge omics technologies, including single-cell RNA sequencing, whole-genome sequencing, and spatial transcriptomics to map and localise genes expressed in the tissue. The platform provides unique insights into individual cell properties and their interactions within tissues. The extensive collection of data is freely accessible through the platform's website. "The Single Cell Atlas not only saves time and resources but also fosters a collaborative environment for scientists from diverse fields, paving the way for new discoveries and innovations," says the study's first author Lu Pan, researcher at the Institute of Environmental Medicine, Karolinska Institutet, Sweden. Looking ahead, the team plans to refine the SCA by introducing more detailed analyses and annual updates. These enhancements will fill gaps in tissue representation and expand the sample size, allowing for more precise research. "The creation of the SCA marks a significant step forward in biomedical research," says the study's last author Xuexin Li, researcher at the Department of Physiology and Pharmacology (previously at the Department of Medical Biochemistry and Biophysics), Karolinska Institutet. "Our goal is to continually enrich the atlas, making it an invaluable resource for understanding human health and disease." The research was done in collaboration with China Medical University and several other international collaboration partners in The Single Cell Atlas Consortium. The study was financed by Karolinska Institutet and the KI Network Medicine Global Alliance (KI NMA). Coauthor Volker Lauschke is CEO and shareholder of HepaPredict AB, co-founder and shareholder of PersoMedix AB, and discloses consultancy work for Enginzyme AB. The other authors declare that they have no competing interests.

A new study suggests that readily available PET scanning could enable a whole-body analysis of the effects of systemic STING-activating therapy in humans, potentially providing a diagnostic tool to guide clinical development of this treatment approach. Stimulator of interferon genes, or STING, helps regulate immune activation. Thus, drugs that activate STING are being tested as a form of cancer immunotherapy and for treating certain infections. Findings from this study reveal previously unknown functional links between STING signaling and immunometabolism. They also suggest that positron emission tomography (PET) imaging could provide a widely accessible approach to measure the pharmacodynamic effects of using STING-activating drugs. Oral and IV administration of STING-activating drugs stimulate potent anti-tumor responses in mouse models of cancer, suggesting this as a possible strategy for human therapy. Until now, however, researchers have not had a way to determine the magnitude, duration and location of immune activation. This research, led by UCLA Jonsson Comprehensive Cancer Center investigators, investigated whether systemic STING activation induces metabolic alterations in immune cells that can be visualized by PET imaging. Lab mice were treated with systemic STING agonists and later imaged with PET scans using standard fluorodeoxyglucose (FDG) radiotracing. Immune cells from the spleen were analyzed by RNA sequencing and flow cytometry. The amount of tracer in B and T lymphocytes was measured. In mice bearing prostate or pancreas cancer tumors, the effects of STING agonist treatment on tracer uptake, T-lymphocyte activation marker levels, and tumor growth were evaluated. Systemic delivery of STING-activating drugs in mice significantly increased PET tracer uptake in the spleen. Analyses of immune cells indicated an increase of tracer in both T and B lymphocytes correlated with the induction of immune cell activation markers. In tumor-bearing mice, STING agonist administration significantly delayed tumor growth and increased radiotracer uptake in secondary lymphoid glands. In addition to identifying previously unknown functional links between STING signaling and immunometabolism, the study suggests that readily available PET scanning could enable a whole-body analysis of the effects of systemic STING-activating therapy in humans. This could potentially provide a diagnostic tool guiding clinical development of this treatment approach. "A new generation of STING agonists have broadened the available routes of administration to include systemic immune activation and are thus moving quickly in the clinical setting of cancer immunotherapy," said co-first co-author Hailey Lee, a graduate student in the laboratory of Dr. Caius Radu, a professor in the Molecular and Medical Pharmacology and Surgery Departments at UCLA and a member of the UCLA Jonsson Comprehensive Cancer Center. Radu, the article's senior author, said, "Given that overstimulation of the immune system could lead to potential toxic side effects for STING agonists, significant questions remain in regard to optimizing the correct dose and treatment schedule for individual patients. Our recent investigation into the identification of a clinically applicable biomarker highlights PET as a readout for measuring STING agonist-induced immune activation in both the preclinical and clinical settings." Co-first author Thuc Le, an adjunct professor of molecular and medical pharmacology at UCLA, added, "Such imaging tools can guide the dosing and scheduling of STING agonists to minimize the risk of immune overstimulation while still retaining therapeutic efficacy. We hope our findings will impact the clinical application of STING agonists." Co-first authors Thuc Le and Hailey Lee are UCLA researchers, as are Evan Abt, Khalid Rashid, Amanda Creech, Liu Wei, Amanda Labora, Charlotte Chan, Eric Sanchez, Daniel Karin, Luyi Li, Nanping Wu, Christine Mona, Giuseppe Carlucci, Willy Hugo, Ting-Ting Wu, Timothy Donahue, Johannes Czernin, and corresponding author Caius Radu. Keke Liang is with China Medical University in Shenyang, China. Jing Cui is with Huazhong University of Science and Technology in Hubei, China. Arthur Cho is with Yonsei University College of Medicine in Seoul, South Korea. Kriti Kriti is with Elucidata Corp. in Cambridge, Massachusetts.