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Combined Blockade of TIGIT and CD39 or A2AR Enhances NK-92 Cell-Mediated Cytotoxicity in AML

Standard

Combined Blockade of TIGIT and CD39 or A2AR Enhances NK-92 Cell-Mediated Cytotoxicity in AML. / Brauneck, Franziska; Seubert, Elisa; Wellbrock, Jasmin; Schulze Zur Wiesch, Julian; Duan, Yinghui; Magnus, Tim; Bokemeyer, Carsten; Koch-Nolte, Friedrich; Menzel, Stephan; Fiedler, Walter.

in: INT J MOL SCI, Jahrgang 22, Nr. 23, 12919, 29.11.2021.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Brauneck, F, Seubert, E, Wellbrock, J, Schulze Zur Wiesch, J, Duan, Y, Magnus, T, Bokemeyer, C, Koch-Nolte, F, Menzel, S & Fiedler, W 2021, 'Combined Blockade of TIGIT and CD39 or A2AR Enhances NK-92 Cell-Mediated Cytotoxicity in AML', INT J MOL SCI, Jg. 22, Nr. 23, 12919. https://doi.org/10.3390/ijms222312919

APA

Brauneck, F., Seubert, E., Wellbrock, J., Schulze Zur Wiesch, J., Duan, Y., Magnus, T., Bokemeyer, C., Koch-Nolte, F., Menzel, S., & Fiedler, W. (2021). Combined Blockade of TIGIT and CD39 or A2AR Enhances NK-92 Cell-Mediated Cytotoxicity in AML. INT J MOL SCI, 22(23), [12919]. https://doi.org/10.3390/ijms222312919

Vancouver

Brauneck F, Seubert E, Wellbrock J, Schulze Zur Wiesch J, Duan Y, Magnus T et al. Combined Blockade of TIGIT and CD39 or A2AR Enhances NK-92 Cell-Mediated Cytotoxicity in AML. INT J MOL SCI. 2021 Nov 29;22(23). 12919. https://doi.org/10.3390/ijms222312919

Bibtex

@article{e629c6fd771840639416873c388cb2a5,
title = "Combined Blockade of TIGIT and CD39 or A2AR Enhances NK-92 Cell-Mediated Cytotoxicity in AML",
abstract = "This study aimed to characterize different natural killer (NK) cell phenotypes on bone marrow and peripheral blood cells from acute myeloid leukemia (AML) patients and healthy donors (HDs). Our data show that CD56dimCD16- and CD56brightCD16- NK cells represent the predominant NK cell subpopulations in AML, while the CD56dimCD16+ NK cells are significantly reduced compared to HDs. Moreover, TIGIT+ and PVRIG+ cells cluster on the CD56dimCD16+ subset whereas CD39+ and CD38+ cells do so on CD56brightCD16- NK cells in AML. Furthermore, functional effects of (co-)blockade of TIGIT and CD39 or A2AR on NK cell functionality were analyzed. These experiments revealed that the single blockade of the TIGIT receptor results in an increased NK-92 cell-mediated killing of AML cells in vitro. Combined targeting of CD39 or A2AR significantly augments the anti-TIGIT-mediated lysis of AML cells. Our data indicate that distinct NK cell subsets in AML exhibit different immunosuppressive patterns (via the TIGIT/PVRIG receptors and the purinergic pathway). In summary, we conclude that TIGIT, CD39, and A2AR constitute relevant inhibitory checkpoints of NK cells in AML patients. A combinatorial blockade synergistically strengthens NK-92 cell-mediated cytotoxicity. As inhibitors of TIGIT, CD39, and A2AR are clinically available, studies on their combined use could be conducted in the near future.",
author = "Franziska Brauneck and Elisa Seubert and Jasmin Wellbrock and {Schulze Zur Wiesch}, Julian and Yinghui Duan and Tim Magnus and Carsten Bokemeyer and Friedrich Koch-Nolte and Stephan Menzel and Walter Fiedler",
year = "2021",
month = nov,
day = "29",
doi = "10.3390/ijms222312919",
language = "English",
volume = "22",
journal = "INT J MOL SCI",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "23",

}

RIS

TY - JOUR

T1 - Combined Blockade of TIGIT and CD39 or A2AR Enhances NK-92 Cell-Mediated Cytotoxicity in AML

AU - Brauneck, Franziska

AU - Seubert, Elisa

AU - Wellbrock, Jasmin

AU - Schulze Zur Wiesch, Julian

AU - Duan, Yinghui

AU - Magnus, Tim

AU - Bokemeyer, Carsten

AU - Koch-Nolte, Friedrich

AU - Menzel, Stephan

AU - Fiedler, Walter

PY - 2021/11/29

Y1 - 2021/11/29

N2 - This study aimed to characterize different natural killer (NK) cell phenotypes on bone marrow and peripheral blood cells from acute myeloid leukemia (AML) patients and healthy donors (HDs). Our data show that CD56dimCD16- and CD56brightCD16- NK cells represent the predominant NK cell subpopulations in AML, while the CD56dimCD16+ NK cells are significantly reduced compared to HDs. Moreover, TIGIT+ and PVRIG+ cells cluster on the CD56dimCD16+ subset whereas CD39+ and CD38+ cells do so on CD56brightCD16- NK cells in AML. Furthermore, functional effects of (co-)blockade of TIGIT and CD39 or A2AR on NK cell functionality were analyzed. These experiments revealed that the single blockade of the TIGIT receptor results in an increased NK-92 cell-mediated killing of AML cells in vitro. Combined targeting of CD39 or A2AR significantly augments the anti-TIGIT-mediated lysis of AML cells. Our data indicate that distinct NK cell subsets in AML exhibit different immunosuppressive patterns (via the TIGIT/PVRIG receptors and the purinergic pathway). In summary, we conclude that TIGIT, CD39, and A2AR constitute relevant inhibitory checkpoints of NK cells in AML patients. A combinatorial blockade synergistically strengthens NK-92 cell-mediated cytotoxicity. As inhibitors of TIGIT, CD39, and A2AR are clinically available, studies on their combined use could be conducted in the near future.

AB - This study aimed to characterize different natural killer (NK) cell phenotypes on bone marrow and peripheral blood cells from acute myeloid leukemia (AML) patients and healthy donors (HDs). Our data show that CD56dimCD16- and CD56brightCD16- NK cells represent the predominant NK cell subpopulations in AML, while the CD56dimCD16+ NK cells are significantly reduced compared to HDs. Moreover, TIGIT+ and PVRIG+ cells cluster on the CD56dimCD16+ subset whereas CD39+ and CD38+ cells do so on CD56brightCD16- NK cells in AML. Furthermore, functional effects of (co-)blockade of TIGIT and CD39 or A2AR on NK cell functionality were analyzed. These experiments revealed that the single blockade of the TIGIT receptor results in an increased NK-92 cell-mediated killing of AML cells in vitro. Combined targeting of CD39 or A2AR significantly augments the anti-TIGIT-mediated lysis of AML cells. Our data indicate that distinct NK cell subsets in AML exhibit different immunosuppressive patterns (via the TIGIT/PVRIG receptors and the purinergic pathway). In summary, we conclude that TIGIT, CD39, and A2AR constitute relevant inhibitory checkpoints of NK cells in AML patients. A combinatorial blockade synergistically strengthens NK-92 cell-mediated cytotoxicity. As inhibitors of TIGIT, CD39, and A2AR are clinically available, studies on their combined use could be conducted in the near future.

U2 - 10.3390/ijms222312919

DO - 10.3390/ijms222312919

M3 - SCORING: Journal article

C2 - 34884723

VL - 22

JO - INT J MOL SCI

JF - INT J MOL SCI

SN - 1661-6596

IS - 23

M1 - 12919

ER -