Immune awakening revealed by peripheral T cell dynamics after one cycle of immunotherapy

Sara Valpione, Elena Galvani, Joshua Tweedy, Piyushkumar A. Mundra, Antonia Banyard, Philippa Middlehurst, Jeff Barry, Sarah Mills, Zena Salih, John Weightman, Avinash Gupta, Gabriela Gremel, Franziska Baenke, Nathalie Dhomen, Paul C. Lorigan, Richard Marais

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Abstract

Our understanding of how checkpoint inhibitors (CPIs) affect T cell evolution is incomplete, limiting our ability to achieve full clinical benefit from these drugs. Here, we analyzed peripheral T cell populations after one cycle of CPI treatment and identified a dynamic awakening of the immune system, as revealed by T cell evolution in response to treatment. We sequenced T cell receptors in plasma cell-free DNA and peripheral blood mononuclear cells and performed phenotypic analysis of peripheral T cell subsets from patients with metastatic melanoma treated with CPIs. We found that early peripheral T cell turnover and T cell receptor repertoire dynamics identified which patients would respond to treatment. Additionally, the expansion of a subset of immune effector peripheral T cells we call TIE cells correlated with response. These events are prognostic and occur within 3 weeks of starting immunotherapy, raising the potential for monitoring patients’ responses by using minimally invasive liquid biopsies.
Original languageEnglish
JournalNature Cancer
Early online date10 Feb 2020
DOIs
Publication statusPublished - 10 Feb 2020

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre

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