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Summary Biology of the response to anti-CTLA-4 involves the dynamics of specific T cell clones. Reasons for clinical success and failure of this treatment are still largely unknown. Here, we quantified the dynamics of the T cell receptor (TCR) repertoire, throughout 4 weeks involving treatment with anti-CTLA-4, in a syngeneic mouse model for colorectal cancer. These dynamics show an initial increase in clonality in tandem with a decrease in diversity, effects which gradually subside. Furthermore, response to treatment is tightly connected to the shared and public parts of the T cell repertoire. We were able to recognize time-dependent behaviors of specific TCR sequences and cell types and to show the response is dominated by specific motifs. We see that a single, specific time point might be useful to inform a physician of the true response to treatmentThe research further highlights the importance of temporal analyses of the immune response., Graphical Abstract, Highlights • Response to ICI is associated with pre-treatment TCR repertoire in mice • TCR repertoire goes through distinct, ICI-dependent changes with time • Tumor size and its response to ICI can be tracked by TCR repertoire metrics • A single time point is found to be a focal point of the immune response, Immunology; Cell Biology: Bioinformatics