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Effects of Adjuvant Anti-PD1 on Atypical/Dysplastic Nevi

Urvashi Joshi

Mentor John Kirkwood, MD and Laura Ferris, MD, PhD
Award Type Resident Fellow Award
Institution University of Pittsburgh
Donor Support In honor of Laura Launikitis
Melanoma is the fifth most common cancer in the U.S. Melanoma is an important public health concern and has a rising number of new cases and deaths per year. Prevention through sunscreens or barrier protection is limited, and no other preventive agents for melanoma have been approved for use. It is vital to develop a more effective prevention method. Atypical/dysplastic nevi (A/DN) are moles that appear abnormal and exhibit irregularity under the microscope. A/DN can develop into melanoma, and an increased number of A/DN is associated with increased risk of developing melanoma. A/DN are a good study target for melanoma prevention. Anti-PD1 therapy is a type of immunotherapy that can be used to treat Stage IIB-IIIC melanoma after surgical removal to reduce the risk of recurrence. This therapy works by removing the brakes from the immune system to allow it to target cancer cells. AntiPD1 therapy may also be useful in preventing melanoma, especially in patients who are at high risk or have multiple A/DN. This research will study the effects of anti-PD1 therapy on A/DN to understand its impact on precursor lesions of melanoma. 30 patients with non-metastatic, Stage IIB-IIIC melanoma receiving treatment with anti-PD1 and with 4 or more A/DN will be included. We will study how anti-PD1 affects A/DN after 3 months of treatment by assessing the changes in appearance of A/DN on the skin and under the microscope, as well as the changes at the molecular, immune, and gene expression level. We hypothesize that A/DN will appear smaller and less pigmented, will regress under the microscope, and will have increased immune cells and decreased expression of genes associated with melanoma. Patients will undergo photographs of the back, magnified dermatoscopic images of select nevi, as well as tape stripping and biopsy of select nevi. This study will help us better understand anti-PD1 as a potential prevention method, and will provide a basis for future melanoma prevention research.