Journal
NATURE CANCER
Volume 1, Issue 2, Pages 210-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s43018-019-0022-x
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Funding
- CRUK [A27412, A22902]
- Harry J. Lloyd Charitable Trust
- Wellcome Trust [100282/Z/12/Z]
- Wellcome Trust [100282/Z/12/Z] Funding Source: Wellcome Trust
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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 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 by using minimally invasive liquid biopsies.
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