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

doi:10.1016/j.isci.2021.102100

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

iScience. 2021 Jan 27;24(2):102100. doi: 10.1016/j.isci.2021.102100. eCollection 2021 Feb 19.

Authors

Hagit Philip¹, Tom Snir¹, Miri Gordin¹, Mikhail Shugay^{2

3}, Alona Zilberberg¹, Sol Efroni¹

Affiliations

¹ The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
² Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
³ Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Moscow, Russia.

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.

Keywords: Cell Biology: Bioinformatics; Immunology.