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


ABSTRACT: 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.

SUBMITTER: Philip H 

PROVIDER: S-EPMC7876555 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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

Philip Hagit H   Snir Tom T   Gordin Miri M   Shugay Mikhail M   Zilberberg Alona A   Efroni Sol S  

iScience 20210127 2


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, respon  ...[more]

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