Here, we apply integrated methods to predict the response of immune checkpoint therapy (ICT) in MMR-deficient tumors including LS through immunohistology and signaling pathway analysis of intratumor transcriptome, and find that the tumor immune signatures are featured with distinct immune cell populations and TLS status and strongly correlated with tumor somatic mutations, cancer development, patient survival, and the response to immunotherapy. This evidence concerns the gene MRC1 and cancer.