(1122-C) Production of peroxynitrite by cancer-associated immune cells can be detected with a fluorescence-based assay
Tuesday, February 6, 2024
12:00 PM – 1:00 PM EST
Location: Exhibit Halls AB
Abstract: The tumor microenvironment (TME) consists of a variety of immune cells, blood vessels, and other cells and molecules that surround primary cancer cells. The interplay between cancer cells and the TME has taken on increasing importance as our understanding of the pro-tumor and anti-tumor effects of immune and other cells have come to light. As the TME is studied more extensively, it has become clear that there is much to learn about this complex system and its interplay with cancer at various stages of progression. This knowledge benefits the development of new therapeutics for treatment of a wide variety of cancers.
Myeloid derived suppressor cells (MDSCs) proliferate extensively in the TME of many cancer patients. These cells contribute to immunosuppression and protect cancers from the immune system in several ways. One way is by generating the reactive oxidant peroxynitrite within the TME, which leads to destructive nitration of protein tyrosine residues. The effects of peroxynitrite within the TME are not yet fully understood, in part, due to a lack of sufficiently sensitive assays to detect this short-lived compound.
Here, we describe an assay that uses the optimized small molecule sensor termed peroxynitrite sensor 3 (PS3) that becomes fluorescent after cleavage by peroxynitrite. We show proof of principle for a microplate reader-based assay that can detect peroxynitrite produced during antibody-dependent cellular phagocytosis using the PS3 fluorescent sensor. Due to the role of peroxynitrite in affecting cell function in the tumor microenvironment, this assay provides a useful tool for better understanding cancer progression and may ultimately assist with the identification of improved treatments that overcome immunosuppression in cancer.