T cells are functionally not impaired in AML: increased PD-1 expression is only seen at time of relapse and correlates with a shift towards the memory T cell compartment

T cell function is crucial for the success of several novel immunotherapeutic strategies for the treatment of acute myeloid leukemia (AML). However, changes in phenotype and function of T cells have been described in various hematologic malignancies, mimicking T cell exhaustion known from chronic vi...

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Bibliographic Details
Published in:Journal of hematology and oncology 2015-07, Vol.8 (1), p.93-93, Article 93
Main Authors: Schnorfeil, Frauke M, Lichtenegger, Felix S, Emmerig, Katharina, Schlueter, Miriam, Neitz, Julia S, Draenert, Rika, Hiddemann, Wolfgang, Subklewe, Marion
Format: Article
Language:English
Subjects:
Antibodies
Antigens
Bone marrow
Cancer
Care and treatment
CD8-Positive T-Lymphocytes - immunology
Chemotherapy
Complications and side effects
Cytokines
Fatigue
Female
Health aspects
Hematology
HIV
Human immunodeficiency virus
Humans
Immunotherapy
Immunotherapy - methods
Infection
Infections
Leukemia
Leukemia, Myeloid, Acute - genetics
Leukemia, Myeloid, Acute - immunology
Ligands
Lymphocytes
Male
Memory (Computers)
Oncology
Patients
Programmed Cell Death 1 Receptor - immunology
Programmed Cell Death 1 Receptor - metabolism
Recurrence
Risk factors
Stem cells
T cell receptors
T cells
Transplantation
Viral infections
Virus diseases
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Summary:T cell function is crucial for the success of several novel immunotherapeutic strategies for the treatment of acute myeloid leukemia (AML). However, changes in phenotype and function of T cells have been described in various hematologic malignancies, mimicking T cell exhaustion known from chronic viral infections. Detailed knowledge about phenotype and function of T cells in AML patients at different stages of the disease is indispensable for optimal development and application of immunotherapeutic strategies for this disease. We used flow cytometry-based assays to characterize T cell phenotype and function in peripheral blood and bone marrow of AML patients at diagnosis, at relapse after intensive chemotherapy, and at relapse after allogeneic stem cell transplantation (SCT). Surface expression of CD244, PD-1, CD160, and TIM-3 was determined, and proliferation and production of IFN-γ, TNF-α, and IL-2 were measured. We detected similar expression of inhibitory molecules on T cells from patients at diagnosis and from age-matched healthy controls. At relapse after SCT, however, PD-1 expression was significantly increased compared to diagnosis, both on CD4(+) and CD8(+) T cells. This pattern was not associated with age and cytomegalovirus (CMV) status but with a shift towards effector memory cells in relapsed AML patients. Proliferation and cytokine production assays did not reveal functional defects in T cells of AML patients, neither at diagnosis nor at relapse. We thus conclude that T cell exhaustion does not play a major role in AML. Immunotherapeutic strategies targeting autologous T cells thus have particularly good prospects in the setting of AML.
ISSN:1756-8722
1756-8722
DOI:10.1186/s13045-015-0189-2