Collaborative Bioinformatics Research with H-SC Student Taylor J. McGee ’23 Highlights New Biomarkers of Melanoma Patient Response to Immunotherapy

Elliott Associate Professor of Biology Dr. Kristian M. Hargadon ’01 recently published an article entitled “Genomic and Transcriptional Changes in IFNg Pathway Genes are Putative Biomarkers of Response to Ipilimumab Immunotherapy in Melanoma Patients” in the journal Expert Review of Clinical Immunology.  This invited article is a Key Paper Evaluation highlighting a seminal paper in the field of tumor immunology from the laboratory of Nobel Laureate Dr. James Allison, who developed the first FDA-approved immunotherapeutic for a cancer treatment strategy known as immune checkpoint blockade.  Since the approval of ipilimumab in 2011, ipilimumab’s success as a therapeutic has spearheaded the development of several other now-approved immune checkpoint inhibitors, all of which function by “unleashing” anti-tumor immune responses that are otherwise restrained in cancer patients.  Though the success of these therapies has led to unprecedented clinical outcomes for many cancer patients, there remain others who either fail to respond to therapy or exhibit disease recurrence after a short response.  The work from Dr. Allison’s group highlighted in Dr. Hargadon’s Key Paper Evaluation was the first to describe defects in genes associated with the IFNg pathway as a mechanism of tumor escape from ipilimumab-associated immune responses.  Specifically, mutations and other alterations to genes that control this pathway in tumor cells were found to drive tumor resistance to therapy-induced immune responses. 

As part of his evaluation of this seminal work, through the College’s Faculty Fellowship Program this past summer Dr. Hargadon conducted additional bioinformatics research with Hampden-Sydney student, Taylor J. McGee ’23, to assess whether non-genomic alterations to the IFNg pathway also correlated with patient response to ipilimumab.  Using clinical data from melanoma patients catalogued in The Cancer Genome Atlas, Dr. Hargadon and Taylor found that RNA levels for several IFNg pathway genes also correlate with patient response to ipilimumab.  These new data indicate that not only are direct changes to IFNg pathway genes associated with tumor resistance to therapy, but so too are alterations in IFNg pathway gene expression levels.  These findings further highlight the significance of the IFNg pathway as a determinant of anti-tumor immune efficacy as first described by Dr. Allison’s group at MD Anderson Cancer Center, and they reveal the potential utility of RNA-level biomarkers associated with this pathway that could be used to predict patient response to immunotherapy in the future.

Taylor McGee, a co-author on this article, is a sophomore at Hampden-Sydney College and plans to pursue his Ph.D. in computational biology following his graduation in 2023.  His ultimate career goal is to apply novel computational models to the study of problems in the field of HIV research.

The article authored by Dr. Hargadon and Taylor can be found at: https://www.tandfonline.com/doi/full/10.1080/1744666X.2021.1847644?scroll=top&needAccess=true