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

Journal of Hematology & Oncology

Marion Subklewe³  Wolfgang Hiddemann¹  Rika Draenert⁴  Julia S. Neitz³  Miriam Schlueter³  Katharina Emmerig³  Felix S. Lichtenegger²  Frauke M. Schnorfeil³ 

[1] Clinical Cooperation Group Pathogenesis of Acute Myeloid Leukemia, Helmholtz Institute Munich, Munich, Germany;Division of Clinical Pharmacology, Department of Internal Medicine IV, Klinikum der Universität München, Munich, Germany;Clinical Cooperation Group Immunotherapy, Helmholtz Institute Munich, Munich, Germany;Division of Clinical Infectiology, Department of Internal Medicine IV, Klinikum der Universität München, Munich, Germany

关键词: Cancer immunotherapy;    Immune checkpoint molecules;    PD-1;    T cell exhaustion;    Acute myeloid leukemia (AML);   

Others  :  1222146
DOI  :  10.1186/s13045-015-0189-2

 received in 2015-02-25, accepted in 2015-07-16,  发布年份 2015

【 摘 要 】

Background

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.

Methods

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.

Results

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.

Conclusion

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.

【 授权许可】

   
2015 Schnorfeil et al.

【 图 表 】

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