Chronic myeloid leukaemia patients at diagnosis and resistant to tyrosine kinase inhibitor therapy display exhausted T-cell phenotype

Br J Haematol. 2022 Sep;198(6):1011-1015. doi: 10.1111/bjh.18302. Epub 2022 Jul 8.

Abstract

The search for novel targets in chronic myeloid leukaemia (CML) is ongoing, to improve treatment efficacy in refractory disease and increase eligibility for tyrosine kinase inhibitor (TKI) discontinuation. Increased frequency of Tregs and effector Tregs was evident at diagnosis, together with increased expression of T-cell exhaustion markers, including in regulatory T cells at diagnosis and in patients with refractory disease. Plasma analysis revealed significantly increased levels of cytokines including tumour necrosis factor (TNF)-a and interleukin (IL)-6 at diagnosis, in keeping with a pro-inflammatory state prior to treatment. We hence demonstrate T-cell exhaustion and a pro-inflammatory state at diagnosis in CML, likely secondary to leukaemia-associated antigenic overload associated with increased disease burden.

Keywords: CML; T cell; T-cell exhaustion; Treg; immune checkpoint; inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / diagnosis
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / genetics
  • Leukemia, Myeloid*
  • Phenotype
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • T-Lymphocytes, Regulatory

Substances

  • Protein Kinase Inhibitors