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

Nat Cancer. 2020 Feb;1(2):210-221. doi: 10.1038/s43018-019-0022-x. Epub 2020 Feb 10.

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."

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Immunologic Factors / therapeutic use
  • Immunotherapy
  • Leukocytes, Mononuclear*
  • Melanoma* / therapy
  • Receptors, Antigen, T-Cell / genetics

Substances

  • Immunologic Factors
  • Receptors, Antigen, T-Cell