<scp>UV</scp>‐induced somatic mutations elicit a functional T cell response in the <scp>YUMMER</scp>1.7 mouse melanoma model

Abstract

Summary Human melanomas exhibit relatively high somatic mutation burden compared to other malignancies. These somatic mutations may produce neoantigens that are recognized by the immune system, leading to an antitumor response. By irradiating a parental mouse melanoma cell line carrying three driver mutations with UVB and expanding a single‐cell clone, we generated a mutagenized model that exhibits high somatic mutation burden. When inoculated at low cell numbers in immunocompetent C57 BL /6J mice, YUMMER 1.7 (Yale University Mouse Melanoma Exposed to Radiation) regresses after a brief period of growth. This regression phenotype is dependent on T cells as YUMMER 1.7 tumors grow significantly faster in immunodeficient Rag1 −/− mice and C57 BL /6J mice depleted of CD 4 and CD 8 T cells. Interestingly, regression can be overcome by injecting higher cell numbers of YUMMER 1.7, which results in tumors that grow without effective rejection. Mice that have previously rejected YUMMER 1.7 tumors develop immunity against higher doses of YUMMER 1.7 tumor challenge. In addition, escaping YUMMER 1.7 tumors are sensitive to anti‐ CTLA ‐4 and anti‐ PD ‐1 therapy, establishing a new model for the evaluation of immune checkpoint inhibition and antitumor immune responses.