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

Hagit Philip, Tom Snir, Miri Gordin, Mikhail Shugay, Alona Zilberberg, Sol Efroni

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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.

Original languageEnglish
Article number102100
JournaliScience
Volume24
Issue number2
DOIs
StatePublished - 19 Feb 2021

Bibliographical note

Publisher Copyright:
© 2021 The Authors

Keywords

  • Cell Biology: Bioinformatics
  • Immunology

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