Abstract
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.
Keywords
citotoksične celice;katepsin X;imunološka sinapsa;cytotoxic cells;cathepsin X;NK-92;immunological synapse;LFA-1;
Data
Language: |
English |
Year of publishing: |
2021 |
Typology: |
1.01 - Original Scientific Article |
Organization: |
UL FFA - Faculty of Pharmacy |
UDC: |
615.37: 616-097 |
COBISS: |
89846019
|
ISSN: |
1422-0067 |
Views: |
84 |
Downloads: |
30 |
Average score: |
0 (0 votes) |
Metadata: |
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Other data
Secondary language: |
Slovenian |
Secondary keywords: |
Imunogenost;Imunoterapija; |
Type (COBISS): |
Article |
Pages: |
str. 1-17 |
Volume: |
ǂVol. ǂ22 |
Issue: |
ǂiss. ǂ24 |
Chronology: |
2021 |
DOI: |
10.3390/ijms222413495 |
ID: |
15417503 |