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

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 b...

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Detalles Bibliográficos
Autores principales: Valpione, Sara, Galvani, Elena, Tweedy, Joshua, Mundra, Piyushkumar A., Banyard, Antonia, Middlehurst, Philippa, Barry, Jeff, Mills, Sarah, Salih, Zena, Weightman, John, Gupta, Avinash, Gremel, Gabriela, Baenke, Franziska, Dhomen, Nathalie, Lorigan, Paul C., Marais, Richard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046489/
https://www.ncbi.nlm.nih.gov/pubmed/32110781
http://dx.doi.org/10.1038/s43018-019-0022-x
Descripción
Sumario: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 T(IE) 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.”