My Mahoney,
Professor and Vice Chair,
Thomas Jefferson University
Dr. Mahoney is a Professor and Vice Chair of Equal Opportunity and Workforce Diversity in the Department of Dermatology and Cutaneous Biology at Thomas Jefferson University in Philadelphia, PA. She also has joint appointment in Biochemistry and Molecular Biology and is a member of the Sidney Kimmel Cancer Center. She received her PhD in Molecular and Cellular Biology from the University of Massachusetts at Amherst and post-doctoral training in Dermatology at the University of Pennsylvania. Dr. Mahoney is part of the leadership team for the Squamous Cell Carcinoma Tumor Ecology and Microenvironment (STEM) Research Group. The goal of her laboratory is to understand, at the molecular and cellular level, how normal signaling events during skin morphogenesis and development are subverted for pathogenic signaling during malignant transformation and disease progression. She focuses on the role of desmosomal cadherins in modulating membrane dynamics and extracellular vesicle release, critical for cell-cell and cell-microenvironment communications.
Biomarkers of an effective Antitumor Response to Immune Checkpoint Inhibitor in Head and Neck Cancer
Wednesday, 15 December 2021 at 11:00
Add to Calendar ▼2021-12-15 11:00:002021-12-15 12:00:00Europe/LondonBiomarkers of an effective Antitumor Response to Immune Checkpoint Inhibitor in Head and Neck CancerExtracellular Vesicles (EVs): Technologies and Biological Investigations in Coronado Island, CaliforniaCoronado Island, CaliforniaSELECTBIOenquiries@selectbiosciences.com
Head and neck squamous cell carcinoma (HNSCC) is the 6th leading cancer worldwide with common risk factors including chronic alcohol and tobacco use as well as human papillomavirus (HPV) infection. Despite the prevalence, there are no clear clinical biomarkers that could delineate normal homeostasis versus tumorigenic processes, HPV positivity, and response to immune checkpoint inhibitors (ICI). In fact, profiling and validation of any cancer biomarkers have proven so complex that HE4 was the last biomarker approved by the FDA for breast cancer in 2009. Emerging as a potentially reliable source for cancer biomarkers are exosomes or small extracellular vesicles (sEVs), which have been shown to play critical roles in cell-to-cell communication and cancer progression. Here, sEVs were isolated from circulating plasma of HNSCC patients and control volunteers by the immunoaffinity ExoRelease method (Clara Biotech) and subjected to bead-based Multiplex profiling of cancer-specific antigens (Luminex). Results were compared to respective total plasma showing substantial differences between the profiles. Interestingly, higher levels of several cancer biomarkers were detected in HNSCC sEVs, particularly in HPV(-) as compared to HPV(+) patients. Most importantly, HE4 associates with HPV(-). In addition to protein biomarkers, we performed small RNAseq for miRNAs in HNSCC sEVs. Here, in a 4-week window of opportunity trial, HNSCC patients received 2 doses of the ICI anti-PD1 mAb, nivolumab. Patients were stratified according to pathologic treatment response, as demonstrated by reduction in tumor size. sEVs isolated from post-treatment tumor cultured supernatant were analyzed by FACS analysis, which confirmed the downregulation of immune checkpoint receptors in responders. Profiling by miRNAseq and analysis by Weka Explorer revealed that 10 miRNAs were strongly correlated with HPV status and 18 miRNAs with response to ICI treatment. KEGG analysis revealed that their targets were associated with pathways in cancer. While the levels of miRNAs did not change in response to treatment, there was a statistically higher level of anti-inflammatory miRNAs, including tumor suppressor miR-146a, in responders versus non-responders. The results from these studies suggest there are new cancer biomarkers that could contribute to better diagnosis and treatment of HNSCC cancer patients.
Add to Calendar ▼2021-12-13 00:00:002021-12-15 00:00:00Europe/LondonExtracellular Vesicles (EVs): Technologies and Biological InvestigationsExtracellular Vesicles (EVs): Technologies and Biological Investigations in Coronado Island, CaliforniaCoronado Island, CaliforniaSELECTBIOenquiries@selectbiosciences.com
Add to Calendar ▼2021-12-15 11:00:002021-12-15 12:00:00Europe/LondonBiomarkers of an effective Antitumor Response to Immune Checkpoint Inhibitor in Head and Neck CancerExtracellular Vesicles (EVs): Technologies and Biological Investigations in Coronado Island, CaliforniaCoronado Island, CaliforniaSELECTBIOenquiries@selectbiosciences.com
