Abstract
The liver resident lymphoid population is featured by the presence of a large number of CD3(+)CD56(+) cells referred as natural T cells. In human hepatocellular carcinoma (HCC) patients, the natural T cells were found to be sharply decreased in tumor (5.871 ± 3.553%) versus non-tumor (14.02 ± 6.151%) tissues. More intriguingly, a substantial fraction of the natural T cells (22.76 ± 18.61%) assumed FOXP3 expression. These FOXP3-expressing CD3(+)CD56(+) cells lost the expression of IFN-γ and perforin, which are critical for the effector function of natural T cells. On the other hand, they acquired surface expression of CD25 and CTLA-4 typically found in regulatory T (Treg) cells. Consistent with the phenotypic conversion, they imposed an inhibitory effect on anti-CD3-induced proliferation of naive T cells. Further studies demonstrated that transforming growth factor β1 (TGF-β1) could effectively induce FOXP3 expression in CD3(+)CD56(+) cells and the cells were thus endowed with a potent immunosuppressive capacity. Finally, Kaplan-Meier analysis revealed that the relative abundance of FOXP3-expressing CD3(+)CD56(+) cells in tumor tissues was significantly correlated with the survival of HCC patients. In conclusion, the present study identified a new type of regulatory immune cells whose emergence in liver cancer tissues may contribute to tumor progression.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adult
-
Aged
-
Aged, 80 and over
-
Biomarkers / metabolism
-
CD3 Complex / genetics
-
CD3 Complex / immunology*
-
CD56 Antigen / genetics
-
CD56 Antigen / immunology*
-
CTLA-4 Antigen / genetics
-
CTLA-4 Antigen / immunology
-
Carcinoma, Hepatocellular / diagnosis
-
Carcinoma, Hepatocellular / immunology*
-
Carcinoma, Hepatocellular / mortality
-
Carcinoma, Hepatocellular / pathology
-
Cell Lineage / drug effects
-
Cell Lineage / immunology
-
Cellular Reprogramming / immunology
-
Female
-
Flow Cytometry
-
Forkhead Transcription Factors / genetics
-
Forkhead Transcription Factors / immunology*
-
Gene Expression
-
Humans
-
Immunophenotyping
-
Interleukin-2 Receptor alpha Subunit / genetics
-
Interleukin-2 Receptor alpha Subunit / immunology
-
Liver Neoplasms / diagnosis
-
Liver Neoplasms / immunology*
-
Liver Neoplasms / mortality
-
Liver Neoplasms / pathology
-
Male
-
Middle Aged
-
Primary Cell Culture
-
Survival Analysis
-
T-Lymphocytes, Cytotoxic / drug effects
-
T-Lymphocytes, Cytotoxic / immunology*
-
T-Lymphocytes, Cytotoxic / pathology
-
T-Lymphocytes, Regulatory / drug effects
-
T-Lymphocytes, Regulatory / immunology*
-
T-Lymphocytes, Regulatory / pathology
-
Transforming Growth Factor beta1 / genetics
-
Transforming Growth Factor beta1 / immunology
-
Transforming Growth Factor beta1 / pharmacology
Substances
-
Biomarkers
-
CD3 Complex
-
CD56 Antigen
-
CTLA-4 Antigen
-
FOXP3 protein, human
-
Forkhead Transcription Factors
-
IL2RA protein, human
-
Interleukin-2 Receptor alpha Subunit
-
NCAM1 protein, human
-
Transforming Growth Factor beta1