UV‐induced somatic mutations elicit a functional T cell response in the YUMMER1.7 mouse melanoma model

• DOI: 10.1111/pcmr.12591
• Publication Date: 2017-04-05T21:42:45Z
• Authors: Jake Wang; Curtis J. Perry; Katrina Meeth; Durga Thakral; William Damsky; Goran Micevic; Susan Kaech; Kim Blenman; Marcus Bosenberg
• Keywords: 0303 health sciences; Ultraviolet Rays; T-Lymphocytes; Green Fluorescent Proteins; Mitosis; Apoptosis; 3. Good health; Mice, Inbred C57BL; Disease Models, Animal; 03 medical and health sciences; Mutation; Exome Sequencing; Animals; Melanoma

Human melanomas exhibit relatively high somatic mutation burden compared to other malignancies. These mutations may produce neoantigens that are recognized by the immune system, leading an antitumor response. By irradiating a parental mouse melanoma cell line carrying three driver with UVB and expanding single-cell clone, we generated mutagenized model exhibits burden. When inoculated at low numbers in immunocompetent C57BL/6J mice, YUMMER1.7 (Yale University Mouse Melanoma Exposed Radiation) regresses after brief period of growth. This regression phenotype is dependent on T cells as tumors grow significantly faster immunodeficient Rag1-/- mice depleted CD4 CD8 cells. Interestingly, can be overcome injecting higher YUMMER1.7, which results without effective rejection. Mice have previously rejected develop immunity against doses tumor challenge. In addition, escaping sensitive anti-CTLA-4 anti-PD-1 therapy, establishing new for evaluation checkpoint inhibition responses.