Congratulations to Anthony Spinella on a successful defense!
Congratulations to Anthony Spinella on successfully defending his PhD dissertation entitled Age-Associated Alterations in Head and Neck Cancer!
Anthony is a member of the Varelas Lab in BU’s Department of Biochemistry & Cell Biology. In 2024, he was selected to present a research talk at the FASEB Hippo Pathway in Biology and Diseases Conference in Melbourne, FL, where he discussed his work on YAP-TEAD blockade and its role in restoring age-associated immune evasion in oral squamous cell carcinoma. He also presented a selected research talk at the 2024 Boston University School of Medicine MD-PhD Annual Retreat. Additionally, Spinella was awarded Best Poster Presentation at the Biochemistry & Cell Biology Department Annual Retreat at BUSM. In 2023, he gave a selected research talk at the American Physician Scientist Association Northeast Regional Meeting. In 2022, Spinella was honored with the Best Lightning Talk Award at the Genome Science Institute 2022 Research Symposium and also won Best Poster Presentation at the 2022 Biochemistry Department Annual Retreat at BUSM.
Anthony was awarded an F30 by the National Institute of Aging, focused on defining age-associated alterations in oral squamous cell carcinoma. Anthony was also awarded a Student Seed Grant by the Boston University Center for Multiscale and Translational Mechanobiology to explore the mechanical properties of the oral tumor microenvironment in aged tissues.
Congratulations again, Anthony, and we wish you all the best moving forward. 🎉
Abstract Summary:
Head and neck squamous cell carcinomas (HNSCC) are the seventh most common cancers globally with poor survival rates and largely ineffective pharmacological treatments. Despite older age being associated with worse survival for HNSCC, most preclinical cancer studies focus on outcomes in young animals, potentially contributing to the limited understanding and treatment strategies for these cancers. To test the influence of age on HNSCC, we utilized carcinogen-induced and syngeneic orthotopic isograft models of HNSCC, performing hemi-lingual injections of murine oral squamous cell carcinoma cells that phenocopy tobacco-driven HNSCC in young and old mice. Old animals exhibited more rapid tumor growth, reduced intra-tumoral immune infiltration, and were enriched for transcriptionally-distinct, immune-evasive tumor cell populations. We observed that older age promotes malignant features in oral lesions. Additionally, we identified an enrichment of an age-associated, immune-evasive carcinoma cell population that coincided with reduced immune infiltration in tumors in old mice, molecular features that corresponded to reduced immune infiltration in human HNSCC. We further identified an age-associated, pro-fibrotic fibroblast population in the aged oral microenvironment that corresponded to elevated collagen deposition and elevated yes-associated protein (YAP) and TEA-domain transcription factor family (TEAD) activity in oral carcinoma cells in old mice. We demonstrated that targeting YAP-TEAD activity restored the immunogenicity of oral carcinoma cells, enhancing immune infiltration and tumor clearance in old mice. In additional studies, we demonstrated that correcting absent chemokine signaling in old mice and could restore intra-tumoral immune infiltration to promote tumor clearance and that induction of an age-associated, fibrotic stroma in young mice could recapitulate both the growth dynamics and immune-evasive phenotypes in oral carcinoma cells observed in old mice. Overall, these studies highlight the critical importance that aging plays in directing tumor biology in HNSCC, that YAP-TEAD contribute to mediating these dynamics, and that targeting age-associated alterations in the carcinoma cell, immune, or stromal compartments could serve as viable avenues for therapeutic intervention to improve outcomes for older HNSCC patients.