{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["8(1)"],"submitter":["Hosoi A"],"pubmed_abstract":["To facilitate the optimization of cancer immunotherapy lacking immune-related adverse events, we performed TCR repertoire analysis of tumor-infiltrating CD8+ T-cells in B16 melanoma-bearing mice receiving anti-PD-1, anti-CTLA-4, anti-4-1BB, anti-CD4 or a combination of anti-PD-1 and 4-1BB antibodies. Although CD8+ T-cells in the tumor were activated and expanded to a greater or lesser extent by these therapies, tumor growth suppression was achieved only by anti-PD-1, anti-PD-1/4-1BB combined, or by anti-CD4 treatment, but not by anti-CTLA-4 or anti-4-1BB monotherapy. Increased CD8+ T cell effector function and TCR diversity with enrichment of certain TCR clonotypes in the tumor was associated with anti-tumor effects. In contrast, polyclonal activation of T-cells in the periphery was associated with tissue damage. Thus, optimal combination therapy increases TCR diversity with extended activation of selective CD8+ T-cells specifically in the tumor but not in the periphery. Incorporation of the concept of evenness for the TCR diversity is proposed."],"journal":["Scientific reports"],"pagination":["1058"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5773695"],"repository":["biostudies-literature"],"pubmed_title":["Increased diversity with reduced \"diversity evenness\" of tumor infiltrating T-cells for the successful cancer immunotherapy."],"pmcid":["PMC5773695"],"pubmed_authors":["Matsushita H","Nagaoka K","Suzuki R","Kitaura K","Aoki S","Morikawa T","Hosoi A","Matsushima K","Ueha S","Iino T","Takeda K","Kubo M","Kakimi K"],"additional_accession":[]},"is_claimable":false,"name":"Increased diversity with reduced \"diversity evenness\" of tumor infiltrating T-cells for the successful cancer immunotherapy.","description":"To facilitate the optimization of cancer immunotherapy lacking immune-related adverse events, we performed TCR repertoire analysis of tumor-infiltrating CD8+ T-cells in B16 melanoma-bearing mice receiving anti-PD-1, anti-CTLA-4, anti-4-1BB, anti-CD4 or a combination of anti-PD-1 and 4-1BB antibodies. Although CD8+ T-cells in the tumor were activated and expanded to a greater or lesser extent by these therapies, tumor growth suppression was achieved only by anti-PD-1, anti-PD-1/4-1BB combined, or by anti-CD4 treatment, but not by anti-CTLA-4 or anti-4-1BB monotherapy. Increased CD8+ T cell effector function and TCR diversity with enrichment of certain TCR clonotypes in the tumor was associated with anti-tumor effects. In contrast, polyclonal activation of T-cells in the periphery was associated with tissue damage. Thus, optimal combination therapy increases TCR diversity with extended activation of selective CD8+ T-cells specifically in the tumor but not in the periphery. Incorporation of the concept of evenness for the TCR diversity is proposed.","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Jan","modification":"2025-04-04T11:30:58.502Z","creation":"2019-03-26T22:58:38Z"},"accession":"S-EPMC5773695","cross_references":{"pubmed":["29348598"],"doi":["10.1038/s41598-018-19548-y"]}}