Acute Conditioning of Antigen-Expanded CD8(+) T Cells via the GSK3β-mTORC Axis Differentially Dictates Their Immediate and Distal Responses after Antigen Rechallenge
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F20%3A10418888" target="_blank" >RIV/00216208:11130/20:10418888 - isvavai.cz</a>
Alternative codes found
RIV/00064203:_____/20:10418888
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=0FwRQEiszN" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=0FwRQEiszN</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3390/cancers12123766" target="_blank" >10.3390/cancers12123766</a>
Alternative languages
Result language
angličtina
Original language name
Acute Conditioning of Antigen-Expanded CD8(+) T Cells via the GSK3β-mTORC Axis Differentially Dictates Their Immediate and Distal Responses after Antigen Rechallenge
Original language description
CD8(+) T cells protect against tumors and intracellular pathogens. The inflammatory cytokines IL-2, IL-15, and IL-7 are necessary for their expansion. However, elevated serum levels of these cytokines are often associated with cancer, poorer prognosis of cancer patients, and exhaustion of antigen-expanded CD8(+) T cells. The impact of acute conditioning of antigen-expanded CD8(+) T cells with these cytokines is unknown. Here, we generated antigen-expanded CD8(+) T cells using dendritic cells and PC-3 cells. The cells were acutely (18-24 h) conditioned with IL-2 and either the GSK3β inhibitor TWS119, the mTORC1 inhibitor rapamycin, or the mTORC1/2 inhibitor Torin1, then their immediate and post-re-expansion (distal) cytokine responses after antigen rechallenge were evaluated. We found that acute IL-2 conditioning upregulated the immediate antigen-induced cytokine response of the tested cells. Following their re-expansion, however, the cells showed a decreased cytokine response. These IL-2 conditioning-mediated impacts were counteracted with TWS119 or rapamycin but not with Torin1. Our data revealed that the acute conditioning of antigen-expanded CD8(+) T cells with IL-2 modulates the GSK3β-mTORC signaling axis. This modulation differentially affected the immediate and distal cytokine responses of the cells. The acute targeting of this signaling axis could, therefore, represent a novel strategy for the modulation of antigen-expanded CD8(+) T cells.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30102 - Immunology
Result continuities
Project
<a href="/en/project/NV16-28135A" target="_blank" >NV16-28135A: Preparation of polyclonal cancer-specific T-cells for adoptive cellular immunotherapy of prostate cancer</a><br>
Continuities
S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cancers
ISSN
2072-6694
e-ISSN
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Volume of the periodical
12
Issue of the periodical within the volume
12
Country of publishing house
CH - SWITZERLAND
Number of pages
22
Pages from-to
3766
UT code for WoS article
000601867300001
EID of the result in the Scopus database
2-s2.0-85097833496