Development of skin leukoderma (LEU) is associated with a positive response to immunotherapy with checkpoint inhibitors in melanoma patients. Thus, we hypothesized that T cell hallmarks in patients who developed LEU could predict patient’s response to checkpoint inhibitors. To this extend, we analyzed T cells from peripheral blood of melanoma patients, classified as responders with LEU, responders without LEU, or no responders, throughout the treatment with anti-PD1 antibodies. We found that occurrence of LEU was associated with reduction of MAIT, Th17 and T-reg cell frequency in the blood. High frequency of CD4+ lymphocytes before treatment could predict LEU development during therapy. We also characterized by immunofluorescence the presence of these T cells in the primary melanoma and LEU of the same patient. It is a common belief that T cells directed against antigens shared by primary melanoma cells and normal melanocytes are responsible for LEU onset. So, we sequenced TCR of T cells present in primary melanoma and LEU biopsy of the same patient. However, we found that TCR sequences in LEU lesions were different from those in the primary melanoma. Only rarely the same TCR sequences were cross-present in both tissues. These data show that LEU onset is not due to reactivation of clones previously present in the primary tumor lesion and that anti-PD-1 therapy induces an immune response against novel antigens that leads to both tumor clearance and LEU development in genetically-predisposed patients.

ESDR443 - T-cell repertoire in metastatic melanoma patients developing skin leukoderma after treatment with checkpoint inhibitors

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.