In summary, in this study, we developed an anti-PD-1-responsive melanoma mouse model that underwent colitis during anti-PD-1 treatment, combined with scRNA-seq data of patients, we analyze the cellular and molecular mechanisms of anti-PD-1 induced colitis, particularly focus on CD8+ lymphocytes, we also provided a therapeutic regimen that combined sirolimus with anti-PD-1, sirolimus played a pivotal role not only in abating immune toxicities induced by anti-PD-1 immunotherapy but in enhancing anti-tumor responses in the tumor environment. Here, CD8A is linked to melanoma.