Specific T-cell immune responses against colony-forming cells including leukemic progenitor cells of AML patients were increased by immune checkpoint inhibition

Item Type:	Article
Title:	Specific T-cell immune responses against colony-forming cells including leukemic progenitor cells of AML patients were increased by immune checkpoint inhibition
Creators Name:	Greiner, J. and Götz, M. and Hofmann, S. and Schrezenmeier, H. and Wiesneth, M. and Bullinger, L. and Döhner, H. and Schneider, V.
Abstract:	The efficacy of immunotherapies in cancer treatment becomes more and more apparent not only in different solid tumors but also in hematological malignancies. However, in acute myeloid leukemia (AML), mechanisms to increase the efficacy of immunotherapeutic approaches have to be further elucidated. Targeting leukemic progenitor and stem cells (LPC/LSC) by specific CTL, for instance, in an adjuvant setting or in minimal residual disease, might be an option to prevent relapse of AML or to treat MRD. Therefore, we investigated the influence of immune checkpoint inhibitors on LAA-specific immune responses by CTL against leukemic myeloid blasts and colony-forming cells including leukemic progenitor cells (CFC/LPC). In functional immunoassays like CFU/CFI (colony-forming units/immunoassays) and ELISpot analysis, we detected specific LAA-directed immune responses against CFC/LPC that are postulated to be the source population of relapse of the disease. The addition of nivolumab (anti-PD-1) significantly increases LAA-directed immune responses against CFC/LPC, no effect is seen when ipilimumab (anti-CTLA-4) is added. The combination of ipilimumab and nivolumab does not improve the effect compared to nivolumab alone. The anti-PD1-directed immune response correlates to PD-L1 expression on progenitor cells. Our data suggest that immunotherapeutic approaches have the potential to target malignant CFC/LPC and anti-PD-1 antibodies could be an immunotherapeutic approach in AML. Moreover, combination with LAA-directed vaccination strategies might also open interesting application possibilities.
Keywords:	Leukemia-Associated Antigens (LAA), Cytotoxic T Lymphocytes (CTL) Responses, Immune Checkpoint Inhibition (ICI), Acute Myeloid Leukemia (AML), Colony-Forming Cells Including Leukemic Progenitor Cells (CFC/LPC), Colony-Forming Immunoassays (CFI)
Source:	Cancer Immunology Immunotherapy
ISSN:	0340-7004
Publisher:	Springer
Volume:	69
Number:	4
Page Range:	629-640
Date:	April 2020
Official Publication:	https://doi.org/10.1007/s00262-020-02490-2
PubMed:	View item in PubMed

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