This study investigates the mechanism of cancer immunoediting, a process by which the immune system controls tumor growth and shapes tumor immunogenicity. The research focuses on the role of T cells in this process, particularly in the context of methylcholanthrene (MCA)-induced sarcomas in immunodeficient mice. Using exome sequencing and other techniques, the study identifies mutant spectrin-β2 as a potential rejection antigen of the d42m1 sarcoma. The findings demonstrate that cancer immunoediting occurs through a T cell-dependent immunoselection process that promotes the outgrowth of tumor cell clones lacking highly antigenic mutant spectrin-β2 and other potential strong antigens. The study also shows that the strong immunogenicity of an unedited tumor can be attributed to the expression of highly antigenic mutant proteins. The results highlight the importance of T cell-dependent immunoselection in the development of escape tumors and provide insights into the molecular mechanisms underlying cancer immunoediting. The study also reveals that the combination of cancer exome sequencing and in silico epitope prediction algorithms can identify highly immunogenic, tumor-specific mutational antigens in unedited carcinogen-induced cancers that serve as targets for the elimination phase of cancer immunoediting. The findings contribute to the understanding of how the immune system interacts with tumors and provide a foundation for the development of individualized cancer immunotherapies targeting tumor-specific antigens.This study investigates the mechanism of cancer immunoediting, a process by which the immune system controls tumor growth and shapes tumor immunogenicity. The research focuses on the role of T cells in this process, particularly in the context of methylcholanthrene (MCA)-induced sarcomas in immunodeficient mice. Using exome sequencing and other techniques, the study identifies mutant spectrin-β2 as a potential rejection antigen of the d42m1 sarcoma. The findings demonstrate that cancer immunoediting occurs through a T cell-dependent immunoselection process that promotes the outgrowth of tumor cell clones lacking highly antigenic mutant spectrin-β2 and other potential strong antigens. The study also shows that the strong immunogenicity of an unedited tumor can be attributed to the expression of highly antigenic mutant proteins. The results highlight the importance of T cell-dependent immunoselection in the development of escape tumors and provide insights into the molecular mechanisms underlying cancer immunoediting. The study also reveals that the combination of cancer exome sequencing and in silico epitope prediction algorithms can identify highly immunogenic, tumor-specific mutational antigens in unedited carcinogen-induced cancers that serve as targets for the elimination phase of cancer immunoediting. The findings contribute to the understanding of how the immune system interacts with tumors and provide a foundation for the development of individualized cancer immunotherapies targeting tumor-specific antigens.