Elizabeth Borden, a fourth-year PhD student in Clinical Translational Sciences at the UA College of Medicine-Phoenix MD/PhD program, has been awarded a National Institutes of Health F30 fellowship from the National Cancer Institute to support her research training on immunoediting in cutaneous squamous cell carcinoma (cSCC).
Immunosuppressed transplant recipients have a 65-253 fold higher risk of developing cSCC and are not good candidates for treatment with immune checkpoint inhibition, as this immunotherapy can lead to non-specific T cell activation and transplant rejection. The ability of T cells to constrain cSCC is demonstrated by the response of 32-46% of immunocompetent patients to immune checkpoint inhibitors. However, cSCC has the potential to evade an active T cell response as demonstrated by the formation of cSCC in immunocompetent patients and resistance to immune checkpoint inhibition in some patients. Prior work suggests that evasion of an active T cell response occurs through the process of immunoediting, in which T cells destroy tumors that present mutated tumor proteins called neoantigens that are recognized by the T cell receptor, and thus select for less immunogenic tumors.
High incidence and poor treatment options for cSCC in immunosuppressed solid organ transplant recipients result in an important unmet clinical need. Under the guidance of her mentor Dr. Karen Hastings at the UA College of Medicine Phoenix and co-mentors Dr. Kenneth Buetow and Dr. Melissa Wilson at the School of Life Sciences at Arizona State University, Elizabeth will compare the mutated peptides and genetic pathways in cSCC from immunosuppressed and immunocompetent individuals to test an innovative approach to identify neoantigens that are recognized by T cells and immune escape mechanisms used by tumors to evade T cell-mediated destruction. This work is anticipated to lead to improved identification of tumor neoantigens which elicit a T cell response and identification of which tumors and which patients will respond to cancer immunotherapy. Dr. Hastings states, “Ms. Borden is a highly-talented MD/PhD student. This award will support her physician-scientist training combining bioinformatics and wet laboratory techniques to address important questions in oncology, her clinical field of interest.”