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CCL 20‐ CCR 6 Cytokine Network Facilitate T reg Activity in Advanced Grades and Metastatic Variants of Hepatocellular Carcinoma
Author(s) -
Li W.M.,
Liu H.R.
Publication year - 2016
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12367
Subject(s) - ccl20 , c c chemokine receptor type 6 , hepatocellular carcinoma , metastasis , immune system , cytokine , immunology , cancer research , cancer , chemokine , biology , liver cancer , medicine , chemokine receptor
Tumour immunity regulates tumour restriction to the site of occurrence. Failure of this balance facilitates tumour spread beyond the primary organ of origin. T regs are known to be recruited in infections, including viral infections like hepatitis B and hepatitis C. Thus, they form a continuum of initial viral infection, an environment of immune suppression by recruitment of T regs , intrinsic viral‐mediated nuclear transformation and carcinogenesis, and thereafter worsening of progress, including metastasis due to the T regs suppressing the cell‐mediated destruction of tumour cells. In this study, we obtained advanced grades of hepatocellular carcinoma ( HCC ) and examined the cytokines that is potentially known to recruit T regs . We examined the expression of CCL 20, the cytokine that recruits T regs . We isolated T regs from HCC samples and examined expression of CCR 6, the receptor for CCL 20 and compared expression in control tissues obtained mainly from subjects with cirrhosis, but no evidence of cancer. The findings of this study indicate that mRNA expression of CCL 20 is significantly enhanced, along with expression of mRNA for the cytokines IL 17 and IL 6. Furthermore, tissue expression of Gamma‐interferon was reduced in HCC . When T regs were isolated from the liver cancer samples, the expression of CCR 6, the only and specific receptor for CCL 20, was upregulated in the cancer tissue derived T regs . Furthermore, STAT 3 levels were significantly increased in these tumour‐derived T regs . This study demonstrates that immune evasion mechanisms are operant in hepatocellular carcinoma through a transcriptional network of CCL 20‐ IL 17‐ IL 6 cytokines that facilitate immune suppression‐mediated cancer cell elimination and metastasis.