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• W2783035773 abstract "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." @default.
• W2783035773 created "2018-01-26" @default.
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• W2783035773 date "2018-01-18" @default.
• W2783035773 modified "2023-10-13" @default.
• W2783035773 title "Increased diversity with reduced “diversity evenness” of tumor infiltrating T-cells for the successful cancer immunotherapy" @default.
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• W2783035773 doi "https://doi.org/10.1038/s41598-018-19548-y" @default.
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