Longitudinal analyses of leukemia-associated antigen-specific CD8+ T cells in patients after allogeneic stem cell transplantation

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Contributors

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment approach for patients with acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL). Graft versus leukemia (GVL) effects, which are exerted by donor T cells directed against leukemic-associated antigens (LAAs), are considered to play a crucial role in disease eradication. Although the expansion of cytotoxic T lymphocytes (CTLs) specific for cytomegalovirus (CMV) in response to an infection has been shown in multiple studies, data on CTLs mediating GVL effects are limited. To evaluate a potential increase or decrease of T lymphocytes specific for LAAs in the setting of allogeneic HSCT, we monitored leukemia-specific CD8 + T cells throughout the first year after HSCT in 18 patients using streptamer technology. A broad panel of promising LAAs was selected: Wilms tumor protein, proteinase 3, receptor for hyaluronan acid-mediated motility, apoptosis regulator Bcl-2, survivin, nucleophosmin, and fibromodulin. T cells specifically directed against AML- or CLL-associated antigens were found at very low frequencies in peripheral blood. Substantial frequencies of LAA-specific T cells could not be measured at any time point by flow cytometry. In contrast, abundant CMV-pp65-specific T cells were detected in CMV-seropositive patient-recipient pairs and an increase prompted by CMV infection could be demonstrated. In conclusion, T lymphocytes with specificities for the aforementioned LAAs can only be detected in minimal quantities in the early phase after allogeneic HSCT.

Details

Original languageEnglish
Pages (from-to)1024-1033.e1
JournalExperimental Hematology
Volume44
Issue number11
Publication statusPublished - Nov 2016
Peer-reviewedYes

External IDs

Scopus 84992602675
PubMed 27473564
researchoutputwizard legacy.publication#72659
researchoutputwizard legacy.publication#78723

Keywords

Keywords

  • Adult, Aged, Amino Acid Sequence, Antigens, Neoplasm/chemistry, Biomarkers, Tumor, CD8-Positive T-Lymphocytes/immunology, Epitopes, T-Lymphocyte/chemistry, Female, Hematopoietic Stem Cell Transplantation/adverse effects, Humans, Leukemia, Lymphocytic, Chronic, B-Cell/immunology, Leukemia, Myeloid, Acute/genetics, Longitudinal Studies, Male, Middle Aged, Peptides/chemistry, Phosphoproteins/immunology, Transplantation, Homologous, Viral Matrix Proteins/immunology