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Cathepsin X activity does not affect NK-target cell synapse but is rather distributed to cytotoxic granules
ID
Jakoš, Tanja
(
Avtor
),
ID
Prunk, Mateja
(
Avtor
),
ID
Pišlar, Anja
(
Avtor
),
ID
Kos, Janko
(
Avtor
)
PDF - Predstavitvena datoteka,
prenos
(3,43 MB)
MD5: 9E2C94342513CA8B7189EE63577B475B
URL - Izvorni URL, za dostop obiščite
https://www.mdpi.com/1422-0067/22/24/13495
Galerija slik
Izvleček
Cathepsin X is a lysosomal peptidase that is involved in tumour progression and represents a potential target for therapeutic interventions. In addition, it regulates important functions of immune cells and is implicated in the modulation of tumour cell–immune cell crosstalk. Selective cathepsin X inhibitors have been proposed as prospective antitumour agents to prevent cancer progression; however, their impact on the antitumour immune response has been overlooked. Previous studies indicate that the migration and adhesion of T cells and dendritic cells are affected by diminished cathepsin X activity. Meanwhile, the influence of cathepsin X inhibition on natural killer (NK) cell function has not yet been explored. Here, we examined the localization patterns of cathepsin X and the role of its inhibitors on the cytotoxicity of cell line NK-92, which is used for adoptive cellular immunotherapy in cancer patients. NK-92 cells depend on lymphocyte function-associated antigen 1 (LFA-1) to form stable immunoconjugates with target cells, providing, in this way, optimal cytotoxicity. Since LFA-1 is a substrate for cathepsin X activity in other types of cells, we hypothesized that cathepsin X could disturb the formation of NK-92 immunoconjugates. Thus, we employed cathepsin X reversible and irreversible inhibitors and evaluated their effects on the NK-92 cell interactions with target cells and on the NK-92 cell cytotoxicity. We show that cathepsin X inhibition does not impair stable conjugate formation or the lytic activity of NK-92 cells. Similarly, the conjugate formation between Jurkat T cells and target cells was not affected by cathepsin X activity. Unlike in previous migration and adhesion studies on T cells, in NK-92 cells cathepsin X was not co-localized with LFA-1 at the plasma membrane but was, rather, redistributed to the cytotoxic granules and secreted during degranulation.
Jezik:
Angleški jezik
Ključne besede:
cytotoxic cells
,
cathepsin X
,
NK-92
,
immunological synapse
,
LFA-1
Vrsta gradiva:
Članek v reviji
Tipologija:
1.01 - Izvirni znanstveni članek
Organizacija:
FFA - Fakulteta za farmacijo
Status publikacije:
Objavljeno
Različica publikacije:
Objavljena publikacija
Leto izida:
2021
Št. strani:
17 str.
Številčenje:
Vol. 22, iss. 24, art. 13495
PID:
20.500.12556/RUL-136937
UDK:
615.37: 616-097
ISSN pri članku:
1422-0067
DOI:
10.3390/ijms222413495
COBISS.SI-ID:
89846019
Datum objave v RUL:
25.05.2022
Število ogledov:
943
Število prenosov:
87
Metapodatki:
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Objavi na:
Gradivo je del revije
Naslov:
International journal of molecular sciences
Skrajšan naslov:
Int. j. mol. sci.
Založnik:
MDPI
ISSN:
1422-0067
COBISS.SI-ID:
2779162
Licence
Licenca:
CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
Povezava:
http://creativecommons.org/licenses/by/4.0/deed.sl
Opis:
To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
Začetek licenciranja:
16.12.2021
Sekundarni jezik
Jezik:
Slovenski jezik
Ključne besede:
citotoksične celice
,
katepsin X
,
imunološka sinapsa
,
imunogenost
,
imunoterapija
Projekti
Financer:
ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
Številka projekta:
P4-0127
Naslov:
Farmacevtska biotehnologija: znanost za zdravje
Financer:
ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
Številka projekta:
J4-1776
Naslov:
Izboljšanje imunoterapevtske vrednosti NK celic z modulacijo cistatina F
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