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

Clinical Immunology : the Official Journal of the Clinical Immunology Society
Long LiuXiao-jun Huang

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.

Citations

Aug 23, 2019·Bone Marrow Transplantation·Meng LvXiao-Jun Huang
May 10, 2020·Journal of Cellular Physiology·Abbas HajifathaliMajid Gholizadeh
Dec 19, 2020·Expert Review of Anticancer Therapy·Amer M ZeidanAndrew M Brunner
Oct 19, 2021·Frontiers in Oncology·Mahnaz RezaeiMazdak Ganjalikhani-Hakemi

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