A T-cell repertoire timestamp is at the core of responsiveness to CTLA-4 blockade

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 repertoire, throughout four 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. Further, 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 a single, specific, time-point might be useful to inform a physician of the true response to treatment. The research further highlights the importance of temporal analyses of the immune response.