CD4+CD25+CD127(low) Regulatory T Cells Play Predominant Anti-Tumor Suppressive Role in Hepatitis B Virus-Associated Hepatocellular Carcinoma

Frontiers in Immunology
Shreya SharmaNirupma Trehanpati

Abstract

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(-ve)FoxP3+ Tregs in HBV-related HCC as compared to non-HBV-HCC. Whole blood immunophenotyping was analyzed by multicolor flow cytometry in patients with HBV-related HCC (HBV-HCC, n = 17), 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+ CD127(low) 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. CD4+CD25+(hi) and Foxp3 expression in CD4+CD25+(hi)CD127(low) 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 + (hi)Tregs. The PD1 expression in CD4 + CD25+(hi) was significantly decreased in the HBVHCC than...Continue Reading

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Citations

Feb 26, 2016·Cancer Immunology, Immunotherapy : CII·Suresh Gopi Kalathil, Yasmin Thanavala
Sep 22, 2015·Frontiers in Immunology·Lynn B Dustin, Nirupma Trehanpati
Jan 22, 2017·Scandinavian Journal of Immunology·N Trehanpati, A K Vyas
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Oct 7, 2020·Cancers·Christo KoleDimitrios Schizas
Oct 22, 2020·BioMed Research International·Qiaofeng DongChunyan Chen
Aug 8, 2021·International Journal of Molecular Sciences·Hyo-Jung Cho, Jae-Youn Cheong

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Methods Mentioned

BETA
biopsy
density gradient centrifugation
PCR

Software Mentioned

ViiA
TreeStar Flow - Jo
Primer

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