PLCL-PEG-PLCL from PolySciTech used in exploration of tumor cytokine interactions

 

Despite years of research, the biological and cellular mechanisms of cancer are not fully understood. Understanding the complex biological pathways and cascades involved in cancer growth and, notably, immunosuppression can unlock potential targets for cancer-specific therapies. Researchers at Johns Hopkins University, Stanford University, University of Ulsan, used PLCL-PEG-PLCL (AK109) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create a gel for delivery of METRNL cytokine as a means to explore the interaction of this cytokine with tumor cells. This research holds promise to improve immunotherapy approaches in the future. Read more: Jackson, Christopher M., Ayush Pant, Wikum Dinalankara, John Choi, Aanchal Jain, Ryan Nitta, Eli Yazigi et al. "The cytokine Meteorin-like inhibits anti-tumor CD8+ T cell responses by disrupting mitochondrial function." Immunity (2024). https://www.cell.com/immunity/abstract/S1074-7613(24)00352-2

“Tumor-infiltrating lymphocyte (TIL) hypofunction contributes to the progression of advanced cancers and is a frequent target of immunotherapy. Emerging evidence indicates that metabolic insufficiency drives T cell hypofunction during tonic stimulation, but the signals that initiate metabolic reprogramming in this context are largely unknown. Here, we found that Meteorin-like (METRNL), a metabolically active cytokine secreted by immune cells in the tumor microenvironment (TME), induced bioenergetic failure of CD8+ T cells. METRNL was secreted by CD8+ T cells during repeated stimulation and acted via both autocrine and paracrine signaling. Mechanistically, METRNL increased E2F-peroxisome proliferator-activated receptor delta (PPARd) activity, causingmitochondrial depolarization and decreased oxidative phosphorylation, which triggered a compensatory bioenergetic shift to glycolysis. Metrnl ablation or downregulation improved the metabolic fitness of CD8+ T cells and enhanced tumor control in several tumor models, demonstrating the translational potential of targeting the METRNL-E2F-PPARd pathway to support bioenergetic fitness of CD8+ TILs.”

PLCL-PEG-PLCL (Cat# AK109): https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AK109#h

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