Volume 2 Supplement 2

Abstracts from the 1st Immunotherapy of Cancer Conference (ITOC1)

Open Access

P20. Lack of T cell exhaustion in acute myeloid leukaemia

  • FM Schnorfeil1,
  • FS Lichtenegger1,
  • K Emmerig1,
  • M Schlüter1,
  • R Draenert2,
  • W Hiddemann3 and
  • M Subklewe3
Journal for ImmunoTherapy of Cancer20142(Suppl 2):P11

https://doi.org/10.1186/2051-1426-2-S2-P11

Published: 12 March 2014

The prognosis of acute myeloid leukemia (AML), particularly when associated with adverse chromosomal or molecular aberrations, is poor due to a high relapse rate after induction chemotherapy. Postremission therapy for elimination of minimal residual disease remains a major challenge. Immunotherapeutic strategies aim at the stimulation of AML-specific immunity, especially of CD8+ T cells. However, the functionality of these cells in AML patients is not well described. T cell exhaustion has been suggested to contribute to immune evasion in various solid and haematological malignancies. Primarily demonstrated in chronic viral infections, exhausted T cells are characterised by an increased expression of several inhibitory molecules, reduced proliferation and an impaired capability of cytokine secretion and cytotoxicity.

To characterise T cell exhaustion in AML, we assessed the phenotype and effector function of CD8+ and CD4+ T cells by flow cytometry. T cells from patients at primary diagnosis, with refractory disease, at relapse and at relapse after allogeneic stem cell transplantation (alloSCT) were analysed for surface expression of CD244, CD160, PD-1, TIM-3 and LAG-3. T cell proliferation and production of the cytokines IFN-γ, TNF-α and IL-2 were measured in response to different stimuli. Results were compared to healthy controls (HCs), while untreated HIV-infected patients served as positive controls for an exhausted T cell state.

In HIV-infected patients, we observed a pronounced upregulation of the inhibitory molecules CD244, CD160 and PD-1 on CD4+ and CD8+ T cells as well as globally impaired cytokine production, clearly indicating T cell exhaustion. In contrast, T cells from AML patients showed an expression pattern of inhibitory surface molecules that was similar to T cells from age-matched HCs. AML patients with a relapse after alloSCT, however, showed remarkably high PD-1 expression on CD4+ and CD8+ T cells, accompanied by a shift from naive to memory T cells. Functionally, no defect in T cell proliferation in any of the AML patient cohorts was detected. Of note, however, we observed a 2-fold decrease in IFN-γ production by CD4+ T cells exclusively in patients at primary diagnosis.

Thus, T cells of AML patients are fully functional. Immunotherapies that aim at eliciting tumour-specific immune responses, e.g. dendritic cell based vaccines, may therefore be particularly suited for AML treatment.

Authors’ Affiliations

(1)
Helmholtz Institute Munich, Clinical Cooperation Group Immunotherapy
(2)
Department of Internal Medicine IV, Klinikum der Universität München
(3)
Department of Internal Medicine III, Klinikum der Universität München

Copyright

© Schnorfeil et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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