Asmi Chakraborty, PhD
Hypoxia as a Driver of the Metastatic Melanoma Glycome and its Immunoevasion Capacity
Summary
Metastatic melanoma (MM) has a dismal 5-year survival rate of 25%. Hence, there is a dire need for biomarkers to predict metastasis and response to immune checkpoint inhibitor (ICI) therapy. Our laboratory discovered that altered MM cell surface sugar structures, glycans, formed by a loss of glycosyltransferase, GCNT2 induce MM growth. Since low tissue oxygen (hypoxia) drives MM growth and resistance to ICI therapy, we hypothesize that MM glycans are evoked by hypoxia and confer ICI resistance. Exciting preliminary data suggest that hypoxia lowers GCNT2 and increases melanoma-initiating cells and MM binding to pro-metastatic galectin (Gal)-3. Further, low GCNT2 correlates with poor MM patient survival and a reduction in ICI response. Studies in this grant are poised to identify novel treatment approaches to improve ICI therapy response based on the identification of unique hypoxia-driven MM glycans and their interaction with Gal3. Results will reveal glycans as biomarkers of MM and implicate Gal-3 targeting to improve ICI efficacy
The PhRMA Foundation Postdoctoral Fellowship has allowed me to pursue a new direction in my project focused on harnessing the metastatic melanoma glycome for improving therapy response in patients
