TIGIT Can Exert Immunosuppressive Effects on CD8+ T Cells by the CD155/TIGIT Signaling Pathway for Hepatocellular Carcinoma In Vitro.
CD8-Positive T-Lymphocytes
/ immunology
Carcinoma, Hepatocellular
/ genetics
Cell Line, Tumor
Coculture Techniques
Cytokines
/ metabolism
Fluorescent Antibody Technique
Humans
Immunohistochemistry
Immunomodulation
/ genetics
Liver Neoplasms
/ genetics
Lymphocyte Activation
/ genetics
Models, Biological
Receptors, Immunologic
/ genetics
Receptors, Virus
/ metabolism
Signal Transduction
Journal
Journal of immunotherapy (Hagerstown, Md. : 1997)
ISSN: 1537-4513
Titre abrégé: J Immunother
Pays: United States
ID NLM: 9706083
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
pubmed:
18
8
2020
medline:
3
9
2021
entrez:
18
8
2020
Statut:
ppublish
Résumé
The efficacy of adoptive cellular immunotherapy against cancer cells is limited due to the presence of immunosuppressive cells within the solid tumor microenvironment. The upregulation of certain coinhibitory receptors may lead to exhaustion of the immune effector cells. T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is an immune inhibitory receptor expressed by regulatory T cells and activated T cells and natural killer cells. The aim of this study was to determine the immunosuppressive effects of CD155/TIGIT signaling on CD8 T cells of adoptive cellular immunotherapy in hepatocellular carcinoma (HCC). Our studies found that CD155 was overexpressed in HCC, and CD155 HCC cells upregulated TIGIT on CD8 T cells, which decreased the secretion of interferon-γ, tumor necrosis factor-α, and interleukin-17A and increased that of interleukin-10 from the effector cells. However, TIGIT blockade or CD155-knockdown reversed the inhibitory effect of HCC cells on CD8 T-cell effector function. These results indicate that TIGIT can exert an immunosuppressive effect on CD8 T cells by modulating cytokine production through CD155, and is a promising target to optimize adoptive cellular immunotherapy against HCC.
Identifiants
pubmed: 32804915
doi: 10.1097/CJI.0000000000000330
pmc: PMC7566309
pii: 00002371-202010000-00002
doi:
Substances chimiques
Cytokines
0
Receptors, Immunologic
0
Receptors, Virus
0
TIGIT protein, human
0
poliovirus receptor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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