| Autor: |
Sharma, Shreya, Khosla, Ritu, David, Paul, Vyas, Ashish, Singh, Dileep, Trehanpati, Nirupma, Rastogi, Archana, Bhardwaj, Ankit, Sahney, Amrish, Maiwall, Rakhi, Sarin, Shiv Kumar |
| Předmět: |
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| Zdroj: |
Frontiers in Immunology; Feb2015, Vol. 6, p1-9, 9p |
| Abstrakt: |
Background: Hepatocellular carcinoma (HCC) is the second leading cause of cancer death worldwide and hepatitis B is one of the commonest causes. T regulatory cells (Tregs) are strong immunomodulators and are likely to play a major role in HCC development. HBV infection is reported to induce expansion of Tregs. We investigated the CD4+CD25+CD127-veFoxP3CTregs in HBV-related HCC as compared to non-HBV-HCC. Patients and Methods: Whole blood immunophenotyping was analyzed by multicolor flowcytometry in patients with HBV-related HCC (HBV-HCC, nD17), non-HBV-HCC (n=22; NASH=16, alcohol-related=6), and chronic hepatitis B infection (CHBV; n=10).Tregs functionality was checked by in vitro suppression assays using CD4+ CD25+ CD127low Tregs. Levels of serum alpha-fetoprotein (AFP), expression of FoxP3, IL-10, PD1,TGF-β, and Notch in Tregs, and liver explants were analyzed by flow cytometry, immunohistochemistry, and quantitative RT-PCR. Results: CD4+CD25+hi and Foxp3 expression in CD4+CD25+hiCD127low was significantly increased (P =0.04, P =0.007) in HBVHCC compared to non-HBVHCC and CHBV patients. HBVHCC also showed high IL-10 and TGF-β secreting CD4 + CD25 + hiTregs. The PD1 expression in CD4+CD25+hi was significantly decreased in the HBVHCC than non-HBVHCC. In HBVHCC, AFP levels were significantly high (median 941, range 2- 727940) than non-HBVHCC (median 13.5, range 2-18,900). In HBVHCC, patients with high AFP (range; 3982-727940 ng/ml) showed positive correlation with Foxp3 expression in CD4+CD25+hi CD127low (r =0.857, P =0.014). Reduced PD1 expression in HBVHCC also had negative correlation with FOXP3 in CD4+CD25+hi CD127low (r =-0.78, P =0.04). However, AFP levels in non-HBVHCC showed negative correlation with (R =-0.67, P =0.005) with CD4+CD25+hi Tregs. Conclusion: Our results demonstrate that CD4+ CD25+hi Tregs from HBVHCC patients have decreased expression of PD1, resulting in higher IL-10 and TGF-β secretion. Increased suppressive ability of Tregs in HBV-related HCC confers increased anti-tumor suppressive response than in non-HBV-HCC. Modulation of Tregs and PD1 may serve as useful therapeutic targets. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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