Allelic polymorphisms of KIRs and antitumor immunity against chronic myeloid leukemia

Immunol Med. 2021 Jun;44(2):61-68. doi: 10.1080/25785826.2020.1796062. Epub 2020 Jul 25.

Abstract

The development of BCR-ABL1 tyrosine kinase inhibitors (TKIs) markedly improved the prognosis of patients with chronic myeloid leukemia (CML). Approximately 50% of patients who achieve deep molecular response (DMR) remain in treatment-free remission (TFR) even after discontinuation of TKIs. Although TKIs may achieve clinical "cure" after TKI treatment for specific periods, there are no reliable biomarkers for predicting the response to TKIs and the probability of TFR in CML. An increase in natural killer (NK) cells in the peripheral blood of TKI-treated CML patients is correlated with better outcomes, suggesting that TKIs induce antitumor NK cell immunity against CML cells. Killer immunoglobulin-like receptors (KIRs) are highly polymorphic NK cell receptors that play important roles in the regulation of immune responses. The identification of allelic polymorphisms of KIRs by next-generation sequencing uncovered novel aspects of KIRs. Here we summarize the current knowledge of the genetic and immunological aspects of KIRs and discuss the association between allelic polymorphisms of KIRs and TKI-treated CML.

Keywords: Chronic myeloid leukemia (CML); antitumor immunity; killer immunoglobulin-like receptor (KIR); natural killer (NK) cell; tyrosine kinase inhibitor (TKI).

Publication types

  • Review

MeSH terms

  • Alleles*
  • Fusion Proteins, bcr-abl / antagonists & inhibitors
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Killer Cells, Natural / immunology*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / immunology*
  • Polymorphism, Genetic*
  • Protein Kinase Inhibitors / therapeutic use
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Receptors, KIR / genetics*
  • Receptors, KIR / immunology*
  • Treatment Outcome

Substances

  • Protein Kinase Inhibitors
  • Receptors, KIR
  • Protein-Tyrosine Kinases
  • Fusion Proteins, bcr-abl