T cell exhaustion characterized by compromised MHC class I and II restricted cytotoxic activity associates with acute B lymphoblastic leukemia relapse after allogeneic hematopoietic stem cell transplantation

Clin Immunol. 2018 May:190:32-40. doi: 10.1016/j.clim.2018.02.009. Epub 2018 Mar 15.

Abstract

Acute B lymphoblastic leukemia (B-ALL) relapse contributes predominantly to the mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the mechanism of B-ALL relapse after allo-HSCT remains unknown. The eradication of leukemia after allo-HSCT largely relies on graft-versus-leukemia (GVL) effects mediated by donor T cells. T cell exhaustion, characterized by the increased expression of inhibitory receptors and impaired function, may suppress GVL effects. In this study, we evaluated whether T cell exhaustion was involved in B-ALL relapse after allo-HSCT. The results showed that CD4+ and CD8+ T cells exhibited increased coexpression of PD-1 and Tim-3, and compromised proliferative capacity, cytokine production and cytotoxic potentials in relapsed patients. Additionally, T cells at the tumor site were more easily exhausted than T cells in the peripheral blood. Moreover, the reversal of T cell exhaustion might correlate with effective anti-leukemic responses after reinduction. These results suggested that T cell exhaustion was associated with B-ALL relapse after allo-HSCT as well as its treatment outcome.

Keywords: Acute B lymphoblastic leukemia; Allogeneic hematopoietic stem cell transplantation; Relapse; T cell exhaustion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Female
  • Hematopoietic Stem Cell Transplantation / methods*
  • Hepatitis A Virus Cellular Receptor 2 / immunology
  • Hepatitis A Virus Cellular Receptor 2 / metabolism
  • Histocompatibility Antigens Class I / immunology*
  • Histocompatibility Antigens Class I / metabolism
  • Histocompatibility Antigens Class II / immunology*
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Programmed Cell Death 1 Receptor / immunology
  • Programmed Cell Death 1 Receptor / metabolism
  • Prospective Studies
  • Recurrence
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Transplantation, Homologous
  • Young Adult

Substances

  • HAVCR2 protein, human
  • Hepatitis A Virus Cellular Receptor 2
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Programmed Cell Death 1 Receptor