Evidence for involvement of clonally expanded CD8(+) T cells in anticancer immune responses in CLL patients following nonmyeloablative conditioning and hematopoietic cell transplantation

T. Kollgaard, S. L. Petersen, Sine Reker Hadrup, T. N. Masmas, T. Seremet, M. H. Andersen, H. O. Madsen, L. Vindeløv, P. thor Straten

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

We have analyzed the clonotype composition of CD8(+) T cells following nonmyeloablative (NMA) conditioning and hematopoietic cell transplantation (HCT), of patients with chronic lymphocytic leukemia (CLL). Consecutive analyses of blood samples taken up to 2 years following HCT, demonstrated that CD8(+) T-cell clonality was highly dynamic in the early phases after HCT, but became more stable after 4 - 5 months. Moreover, donor lymphocyte infusion (DLI) given for disease progression in one of the patients led to establishment of recurrent as well as new T-cell clonotypes. This coincided with disease remission, strongly suggesting that these T cells were engaged with anti-CLL cytotoxicity. To examine the functional capacity of stable clonally expanded T cells after HCT, CD8(+) T cells isolated post-transplant from the recipients were stimulated ex vivo with CLL cells and subsequently analyzed by FACS for surface expression of the marker for cytotoxic activity, CD107a. Stimulation with CLL cells indeed led to surface expression of CD107a, and clonotype analyses of sorted cells demonstrated that CD107a positive T cells were stably expanded following HCT. Our data suggest that clonally expanded CD8(+) T-cell clones participate in the ongoing T-cell response against CLL cells following HCT with NMA conditioning.
Original languageEnglish
JournalLeukemia
Volume19
Issue number12
Pages (from-to)2273-2280
Number of pages8
ISSN0887-6924
DOIs
Publication statusPublished - 2005
Externally publishedYes

Keywords

  • Hematology
  • Cancer Research
  • Chronic lymphocytic leukemia (CLL)
  • Cytotoxic T lymphocyte (CTL)
  • Hematopoitec cell transplantation (HCT)
  • T-cell clonotypes
  • CD8 antigen
  • cyclosporin
  • fludarabine
  • lysosome associated membrane protein 1
  • mycophenolic acid 2 morpholinoethyl ester
  • prednisolone
  • rituximab
  • adoptive immunotherapy
  • adult
  • article
  • blood sampling
  • case report
  • cell isolation
  • cellular immunity
  • chronic lymphatic leukemia
  • clonal variation
  • disease course
  • ex vivo study
  • fluorescence activated cell sorting
  • graft versus host reaction
  • hematopoietic stem cell transplantation
  • human
  • leukemia remission
  • lymphocyte clone
  • lymphocytotoxicity
  • male
  • nonmyeloablative conditioning
  • priority journal
  • recipient
  • suppressor cell
  • CD8-Positive T-Lymphocytes
  • Cell Proliferation
  • Clone Cells
  • Cytotoxicity, Immunologic
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Immunity
  • Leukemia, Lymphocytic, Chronic
  • Longitudinal Studies
  • Lymphocyte Transfusion
  • Lysosomal-Associated Membrane Protein 1
  • Male
  • Middle Aged
  • Transplantation Conditioning
  • Treatment Outcome
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • ONCOLOGY
  • HEMATOLOGY
  • CHRONIC LYMPHOCYTIC-LEUKEMIA
  • MINOR HISTOCOMPATIBILITY ANTIGENS
  • BONE-MARROW-TRANSPLANTATION
  • GRAFT-VERSUS-LEUKEMIA
  • MINIMAL RESIDUAL DISEASE
  • TREATMENT-RELATED MORTALITY
  • HOST-DISEASE
  • GENE
  • QUANTIFICATION
  • RECONSTITUTION
  • chronic lymphocytic leukemia (CLL)
  • hematopoietic cell transplantation ( HCT)
  • cytotoxic T lymphocyte (CTL)
  • Primates Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Humans, Mammals, Primates, Vertebrates) - Hominidae [86215] human common middle age male
  • CD107a
  • CD8
  • 02506, Cytology - Animal
  • 02508, Cytology - Human
  • 10064, Biochemistry studies - Proteins, peptides and amino acids
  • 12512, Pathology - Therapy
  • 15002, Blood - Blood and lymph studies
  • 15004, Blood - Blood cell studies
  • 15006, Blood - Blood, lymphatic and reticuloendothelial pathologies
  • 24003, Neoplasms - Immunology
  • 24004, Neoplasms - Pathology, clinical aspects and systemic effects
  • 24008, Neoplasms - Therapeutic agents and therapy
  • 24010, Neoplasms - Blood and reticuloendothelial neoplasms
  • 34502, Immunology - General and methods
  • 34508, Immunology - Immunopathology, tissue immunology
  • Clinical Immunology
  • Methods and Techniques
  • Oncology
  • chronic lymphocytic leukemia Leukemia, Lymphocytic, Chronic (MeSH) neoplastic disease, immune system disease, blood and lymphatic disease therapy
  • anticancer immune responses
  • Human Medicine, Medical Sciences
  • T cell immune system, blood and lymphatics
  • hematopoietic cell transplantation therapeutic and prophylactic techniques, clinical techniques
  • nonmyeloblative conditioning therapeutic and prophylactic techniques, clinical techniques
  • T cells

Fingerprint Dive into the research topics of 'Evidence for involvement of clonally expanded CD8(+) T cells in anticancer immune responses in CLL patients following nonmyeloablative conditioning and hematopoietic cell transplantation'. Together they form a unique fingerprint.

Cite this