TGF-(3 Decreases NK Cell Mobility and Cytotoxic Efficacy in
Complex in vitro Models of the Leukemia Microenvironment

J 2025

TGF-(3 Decreases NK Cell Mobility and Cytotoxic Efficacy in Complex in vitro Models of the Leukemia Microenvironment

SVUBOVA, Veronika; Lucie JANSTOVA; Marek JEDLICKA; Eva MASINOVA; Jana SZABOVA et al.

Základní údaje

Originální název

TGF-(3 Decreases NK Cell Mobility and Cytotoxic Efficacy in Complex in vitro Models of the Leukemia Microenvironment

Autoři

Vydání

IMMUNOTARGETS AND THERAPY, AUCKLAND, DOVE MEDICAL PRESS LTD, 2025, 2253-1556

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30102 Immunology

Stát vydavatele

Nový Zéland

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.400 v roce 2024

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/25:00143538

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

3D models; TGFbeta; acute myeloid leukemia; bone marrow niche; NK cells; immunotherapy

Štítky

14110132, 14110513, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 23. 1. 2026 11:27, Mgr. Tereza Miškechová

Anotace

V originále

Background: Natural killer (NK) cell-based therapies represent a promising approach for acute myeloid leukemia (AML) relapse, yet their efficacy is hindered by immunosuppressive factors such as transforming growth factor beta (TGF-(3) in the tumor microenvironment. This study investigated the effects of TGF-(3 on NK cell cytotoxicity and migration using 2D and 3D co-culture models that mimic the leukemic microenvironment. Methods: TGF-(3 production was evaluated in AML-derived leukemic cell lines and mesenchymal stromal cells (hTERT-MSCs) using ELISA. Bulk RNA sequencing (RNA-seq) was performed to analyze global gene expression changes in TGF-(3-treated primary human NK cells. NK cell cytotoxicity and migration were assessed in 2D monolayer and 3D spheroid co-cultures containing hTERT-MSCs and leukemic cells using flow cytometry and confocal microscopy. Results: Both leukemic cells and MSCs produced TGF-(3, with increased levels observed in MSCs after co-culture with primary AML blasts. RNA sequencing revealed that TGF-(3 altered key gene pathways associated with NK cell cytotoxicity, adhesion, and migration, supporting its immunosuppressive role. In functional assays, TGF-(3 exposure significantly reduced NK cell-mediated cytotoxicity in a time-dependent manner and impaired NK cell infiltration into 3D spheroids, particularly in models incorporating MSCs. Additionally, MSCs themselves provided a protective environment for leukemic cells, further reducing NK cell effectiveness in 2D co-cultures. Conclusion: TGF-(3 suppresses both NK cell cytotoxicity and migration, limiting their ability to eliminate leukemic cells and infiltrate the bone marrow niche (BMN). These findings provide novel insights into TGF-(3-mediated immune evasion mechanisms and provide important insights for the future design of NK-based immunotherapies and clinical trials.

Citovat

SVUBOVA, Veronika; Lucie JANSTOVA; Marek JEDLICKA; Eva MASINOVA; Jana SZABOVA; Tereza FEGLAROVA; Katerina KUGLEROVA; Veronika BOSÁKOVÁ; Barbora BRODSKA; Kristyna BORAKOVA; David KUNDRAT; Iva TRSOVA; Martina BOHMOVA; Katerina KUZELOVA; Jiri HRDY; Zdenka GASOVA; Jan VYDRA; Michaela DOSTALOVA MERKEROVA; Marcela HORTOVÁ KOHOUTKOVÁ a Jan FRIČ. TGF-(3 Decreases NK Cell Mobility and Cytotoxic Efficacy in Complex in vitro Models of the Leukemia Microenvironment. IMMUNOTARGETS AND THERAPY. AUCKLAND: DOVE MEDICAL PRESS LTD, 2025, roč. 14, June 2025, s. 589-604. ISSN 2253-1556. Dostupné z: https://doi.org/10.2147/ITT.S512700.

@article{2549539,
   author = {Svubova, Veronika and Janstova, Lucie and Jedlicka, Marek and Masinova, Eva and Szabova, Jana and Feglarova, Tereza and Kuglerova, Katerina and Bosáková, Veronika and Brodska, Barbora and Borakova, Kristyna and Kundrat, David and Trsova, Iva and Bohmova, Martina and Kuzelova, Katerina and Hrdy, Jiri and Gasova, Zdenka and Vydra, Jan and Dostalova Merkerova, Michaela and Hortová Kohoutková, Marcela and Frič, Jan},
   article_location = {AUCKLAND},
   article_number = {June 2025},
   doi = {https://doi.org/10.2147/ITT.S512700},
   keywords = {3D models; TGFbeta; acute myeloid leukemia; bone marrow niche; NK cells; immunotherapy},
   language = {eng},
   issn = {2253-1556},
   journal = {IMMUNOTARGETS AND THERAPY},
   title = {TGF-(3 Decreases NK Cell Mobility and Cytotoxic Efficacy in Complex in vitro Models of the Leukemia Microenvironment},
   url = {https://www.dovepress.com/tgf--decreases-nk-cell-mobility-and-cytotoxic-efficacy-in-complex-in-v-peer-reviewed-fulltext-article-ITT},
   volume = {14},
   year = {2025}
}

TY  - JOUR
ID  - 2549539
AU  - Svubova, Veronika - Janstova, Lucie - Jedlicka, Marek - Masinova, Eva - Szabova, Jana - Feglarova, Tereza - Kuglerova, Katerina - Bosáková, Veronika - Brodska, Barbora - Borakova, Kristyna - Kundrat, David - Trsova, Iva - Bohmova, Martina - Kuzelova, Katerina - Hrdy, Jiri - Gasova, Zdenka - Vydra, Jan - Dostalova Merkerova, Michaela - Hortová Kohoutková, Marcela - Frič, Jan
PY  - 2025
TI  - TGF-(3 Decreases NK Cell Mobility and Cytotoxic Efficacy in Complex in vitro Models of the Leukemia Microenvironment
JF  - IMMUNOTARGETS AND THERAPY
VL  - 14
IS  - June 2025
SP  - 589-604
EP  - 589-604
PB  - DOVE MEDICAL PRESS LTD
SN  - 22531556
KW  - 3D models
KW  - TGFbeta
KW  - acute myeloid leukemia
KW  - bone marrow niche
KW  - NK cells
KW  - immunotherapy
UR  - https://www.dovepress.com/tgf--decreases-nk-cell-mobility-and-cytotoxic-efficacy-in-complex-in-v-peer-reviewed-fulltext-article-ITT
N2  - Background: Natural killer (NK) cell-based therapies represent a promising approach for acute myeloid leukemia (AML) relapse, yet their efficacy is hindered by immunosuppressive factors such as transforming growth factor beta (TGF-(3) in the tumor microenvironment. This study investigated the effects of TGF-(3 on NK cell cytotoxicity and migration using 2D and 3D co-culture models that mimic the leukemic microenvironment. Methods: TGF-(3 production was evaluated in AML-derived leukemic cell lines and mesenchymal stromal cells (hTERT-MSCs) using ELISA. Bulk RNA sequencing (RNA-seq) was performed to analyze global gene expression changes in TGF-(3-treated primary human NK cells. NK cell cytotoxicity and migration were assessed in 2D monolayer and 3D spheroid co-cultures containing hTERT-MSCs and leukemic cells using flow cytometry and confocal microscopy. Results: Both leukemic cells and MSCs produced TGF-(3, with increased levels observed in MSCs after co-culture with primary AML blasts. RNA sequencing revealed that TGF-(3 altered key gene pathways associated with NK cell cytotoxicity, adhesion, and migration, supporting its immunosuppressive role. In functional assays, TGF-(3 exposure significantly reduced NK cell-mediated cytotoxicity in a time-dependent manner and impaired NK cell infiltration into 3D spheroids, particularly in models incorporating MSCs. Additionally, MSCs themselves provided a protective environment for leukemic cells, further reducing NK cell effectiveness in 2D co-cultures. Conclusion: TGF-(3 suppresses both NK cell cytotoxicity and migration, limiting their ability to eliminate leukemic cells and infiltrate the bone marrow niche (BMN). These findings provide novel insights into TGF-(3-mediated immune evasion mechanisms and provide important insights for the future design of NK-based immunotherapies and clinical trials.
ER  -

SVUBOVA, Veronika; Lucie JANSTOVA; Marek JEDLICKA; Eva MASINOVA; Jana SZABOVA; Tereza FEGLAROVA; Katerina KUGLEROVA; Veronika BOSÁKOVÁ; Barbora BRODSKA; Kristyna BORAKOVA; David KUNDRAT; Iva TRSOVA; Martina BOHMOVA; Katerina KUZELOVA; Jiri HRDY; Zdenka GASOVA; Jan VYDRA; Michaela DOSTALOVA MERKEROVA; Marcela HORTOVÁ KOHOUTKOVÁ a Jan FRIČ. TGF-(3 Decreases NK Cell Mobility and Cytotoxic Efficacy in Complex in vitro Models of the Leukemia Microenvironment. \textit{IMMUNOTARGETS AND THERAPY}. AUCKLAND: DOVE MEDICAL PRESS LTD, 2025, roč.~14, June 2025, s.~589-604. ISSN~2253-1556. Dostupné z: https://doi.org/10.2147/ITT.S512700.

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