Anngela C. Adams, an MD/PhD candidate in the Clinical Translational Sciences Graduate Program at the University of Arizona College of Medicine Phoenix, has been awarded a prestigious, individual F30 fellowship training grant from the National Cancer Institute (NCI). This grant will support her continued training and research which focuses on investigating the role of neoantigen-specific T cells in cutaneous squamous cell carcinoma (cSCC), using a mouse model she developed in Dr. Karen T. Hastings’ laboratory. Ms. Adams’ research training has been previously supported by the NCI T32 institutional training grant, Interdisciplinary Training in Cancer Biology Research.
To address the need for a clinically relevant mouse cSCC model that can be used to study T cells that recognize mutated peptides in cancers called neoantigens, Ms. Adams completed a 65 week animal study. During this animal study, she exposed mice to solar UV light, using a device she built, and generated cell lines from the tumors that formed. This novel panel of transplantable cSCC cell lines has the benefits of sharing the same etiologic factor, a high UV-signature mutational burden, and driver mutations with human disease. In addition, the transplantable cell lines form tumors rapidly in mice compared to the long-time frame for UV light tumor induction and allow for evaluation of neoantigen-specific T cells.
Under the primary mentorship of Dr. Karen T. Hastings, and co-mentorship from Dr. Clara Curiel-Lewandrowski at the University of Arizona College of Medicine-Tucson, Ms. Adams is using the cSCC mouse model to study T cell responses that constrain cSCC tumor growth. Her work has demonstrated a major role for CD8 T cells and a contributing role for CD4 T cells in controlling cSCC growth. She identified IFN-γ-secreting CD8 T cells within tumors that recognize a neoantigen in the cSCC cell line. Vaccination with this neoantigen decreases cSCC growth, supporting that the immune response to this neoantigen controls tumor growth. Her work shows that neoantigen-specific T cells can constrain cSCC growth in a solar UV light-induced model. This project is anticipated to identify neoantigen characteristics that elicit a T cell response and the features of neoantigen-specific T cell responses that promote tumor rejection. Ms. Adams was selected to give an oral presentation on this work at the International Societies for Investigative Dermatology meeting in Tokyo, Japan in May 2023. Her travel was supported by a grant from the North American Society for Investigative Dermatology.
After Ms. Adams finishes her PhD in the Spring of 2024, she will complete the last two years of medical school and then apply for a dermatology residency. This grant will support her MD/PhD training to prepare for a career as a productive and independent physician-scientist in the field of skin cancer immunology. Ms. Adams’s long-term career goals include: providing insight into the immunological pathways involved in skin cancers, creating the foundation for the development of new treatments for skin cancers, and working to improve the lives of dermatology and cancer patients. Dr. Hastings states, “Ms. Adams has a strong commitment to research and dermatology and has demonstrated a high degree of productivity during her training. I have no doubt that she will be successful in her goal of becoming an investigative dermatologist conducting research on skin cancer.”