Invariant NKT Cells From Donor Lymphocyte Infusions (DLI-iNKTs) Promote ex vivo Lysis of Leukemic Blasts in a CD1d-Dependent Manner

Jahnke S, Schmid H, Secker KA, Einhaus J, Duerr-Stoerzer S, Keppeler H, Schober-Melms I, Schumm M, Handgretinger R, Bethge W, Kanz L, Schneidawind C, Schneidawind D, Baur R (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Frontiers in Immunology Frontiers Research Foundation / Frontiers Media

Book Volume: 10

DOI: 10.3389/fimmu.2019.01542

Abstract

Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative treatment option for hematologic malignancies but relapse remains the most common cause of death. Infusion of donor lymphocytes (DLIs) can induce remission and prolong survival by exerting graft-vs.-leukemia (GVL) effects. However, sufficient tumor control cannot be established in all patients and occurrence of graft-vs.-host disease (GVHD) prevents further dose escalation. Previous data indicate that invariant natural killer T (iNKT) cells promote anti-tumor immunity without exacerbating GVHD. In the present study we investigated lysis of leukemic blasts through iNKT cells from donor-derived lymphocytes for leukemia control and found that iNKT cells constitute about 0.12% of cryopreserved donor T cells. Therefore, we established a 2-week cell culture protocol allowing for a robust expansion of iNKT cells from cryopreserved DLIs (DLI-iNKTs) that can be used for further preclinical and clinical applications. Such DLI-iNKTs efficiently lysed leukemia cell lines and primary patient AML blasts ex vivo in a dose- and CD1d-dependent manner. Furthermore, expression of CD1d on target cells was required to release proinflammatory cytokines and proapoptotic effector molecules. Our results suggest that iNKT cells from donor-derived lymphocytes are involved in anti-tumor immunity after allo-HCT and therefore may reduce the risk of relapse and improve progression-free and overall survival.

Authors with CRIS profile

Rebecca Baur Department of Medicine 5 – Haematology and Oncology

Involved external institutions

Universitätsklinikum Tübingen DE Germany (DE) Universitätsklinikum Magdeburg A.ö.R. DE Germany (DE)

How to cite

APA:

Jahnke, S., Schmid, H., Secker, K.-A., Einhaus, J., Duerr-Stoerzer, S., Keppeler, H.,... Baur, R. (2019). Invariant NKT Cells From Donor Lymphocyte Infusions (DLI-iNKTs) Promote ex vivo Lysis of Leukemic Blasts in a CD1d-Dependent Manner. Frontiers in Immunology, 10. https://dx.doi.org/10.3389/fimmu.2019.01542

MLA:

Jahnke, Simona, et al. "Invariant NKT Cells From Donor Lymphocyte Infusions (DLI-iNKTs) Promote ex vivo Lysis of Leukemic Blasts in a CD1d-Dependent Manner." Frontiers in Immunology 10 (2019).

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