Immune-awakening revealed by peripheral T cell dynamics after one cycle of immunotherapy
Valpione, Sara Galvani, Elena Tweedy, Joshua Mundra, Piyushkumar A Banyard, Antonia Middlehurst, Philippa Barry, Jeff Mills, Sarah Salih, Zena Weightman, John
Valpione, Sara
Galvani, Elena
Tweedy, Joshua
Mundra, Piyushkumar A
Banyard, Antonia
Middlehurst, Philippa
Barry, Jeff
Mills, Sarah
Salih, Zena
Weightman, John
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Abstract
Our understanding of how checkpoint inhibitors (CPI) 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 and identified a dynamic awakening of the immune system revealed by T cell evolution in response to treatment. We sequenced T cell receptors (TCR) in plasma cell-free DNA (cfDNA) and peripheral blood mononuclear cells (PBMC) and performed phenotypic analysis of peripheral T cell subsets from metastatic melanoma patients treated with CPI. We found that early peripheral T cell turnover and TCR 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 using minimally invasive liquid biopsies."
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Date
2020
Publisher
Collections
Keywords
Type
Article
Citation
Valpione S, Galvani E, Tweedy J, Mundra PA, Banyard A, Middlehurst P, et al. Immune-awakening revealed by peripheral T cell dynamics after one cycle of immunotherapy. Nat Cancer. 2020;1:210-21.