Expansion of peripheral and intratumoral regulatory T-cells in hepatocellular carcinoma: A case-control study

Background: Hepatocellular carcinoma (HCC) is notorious for poor prognosis with limited therapeutic options. A better understanding of the role of regulatory T-cells (Tregs) in HCC is important for design of immunotherapy based clinical protocol. The objective of the present study was to evaluate th...

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Main Authors: Sapna Thakur, Anuj Singla, Yogesh Chawla, Arvind Rajwanshi, Naveen Kalra, Sunil K Arora
Format: Article
Language:English
Published: Wolters Kluwer Medknow Publications 2011-01-01
Series:Indian Journal of Pathology and Microbiology
Subjects:
Online Access:http://www.ijpmonline.org/article.asp?issn=0377-4929;year=2011;volume=54;issue=3;spage=448;epage=453;aulast=Thakur
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author Sapna Thakur
Anuj Singla
Yogesh Chawla
Arvind Rajwanshi
Naveen Kalra
Sunil K Arora
author_facet Sapna Thakur
Anuj Singla
Yogesh Chawla
Arvind Rajwanshi
Naveen Kalra
Sunil K Arora
author_sort Sapna Thakur
collection DOAJ
description Background: Hepatocellular carcinoma (HCC) is notorious for poor prognosis with limited therapeutic options. A better understanding of the role of regulatory T-cells (Tregs) in HCC is important for design of immunotherapy based clinical protocol. The objective of the present study was to evaluate the presence of Tregs in tumor microenvironment in patients with HCC compared to chronic hepatitis (CH). Materials and Methods: The frequency of CD4 + CD25 + Treg cells was evaluated from peripheral blood (PB) of 28 patients of HCC and 30 controls including CH cases and healthy donors using flowcytometry. Intratumoral Treg were also analyzed in tissue samples from 17 HCC cases and 15 CH cases. In addition the expression of FOXP3 and CTLA-4 was also studied by RT-PCR. Results: Frequency of CD4 + CD25 + cells in the PBMCs of HCC cases was significantly higher than in HC (10.8 ± 7.64 vs 3.05 ± 1.30, P < 0.005) and CH patients (2.88 ± 1.92, P < 0.005). Also Treg population was significantly higher in HCC tumor microenvironment compared to CH biopsies (15.8 ± 5.32 vs 5.51 ± 3.40, P < 0.05). Expression of FOXP3 and CTLA-4 was also significantly higher in HCC patients ( P < 0.05) compared to CH group. Conclusions: We provide evidence of an increased population of Treg not only in the PB but also in tumor microenvironment of HCC patients, suggesting association of enhanced Treg activity with poor immune responses to tumor antigens. These findings may in future play a significant role in designing immunotherapeutic approaches in HCC.
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spelling doaj.art-02ad67049ad7463e94ff72f763cd85772022-12-21T17:33:20ZengWolters Kluwer Medknow PublicationsIndian Journal of Pathology and Microbiology0377-49292011-01-0154344845310.4103/0377-4929.85073Expansion of peripheral and intratumoral regulatory T-cells in hepatocellular carcinoma: A case-control studySapna ThakurAnuj SinglaYogesh ChawlaArvind RajwanshiNaveen KalraSunil K AroraBackground: Hepatocellular carcinoma (HCC) is notorious for poor prognosis with limited therapeutic options. A better understanding of the role of regulatory T-cells (Tregs) in HCC is important for design of immunotherapy based clinical protocol. The objective of the present study was to evaluate the presence of Tregs in tumor microenvironment in patients with HCC compared to chronic hepatitis (CH). Materials and Methods: The frequency of CD4 + CD25 + Treg cells was evaluated from peripheral blood (PB) of 28 patients of HCC and 30 controls including CH cases and healthy donors using flowcytometry. Intratumoral Treg were also analyzed in tissue samples from 17 HCC cases and 15 CH cases. In addition the expression of FOXP3 and CTLA-4 was also studied by RT-PCR. Results: Frequency of CD4 + CD25 + cells in the PBMCs of HCC cases was significantly higher than in HC (10.8 ± 7.64 vs 3.05 ± 1.30, P < 0.005) and CH patients (2.88 ± 1.92, P < 0.005). Also Treg population was significantly higher in HCC tumor microenvironment compared to CH biopsies (15.8 ± 5.32 vs 5.51 ± 3.40, P < 0.05). Expression of FOXP3 and CTLA-4 was also significantly higher in HCC patients ( P < 0.05) compared to CH group. Conclusions: We provide evidence of an increased population of Treg not only in the PB but also in tumor microenvironment of HCC patients, suggesting association of enhanced Treg activity with poor immune responses to tumor antigens. These findings may in future play a significant role in designing immunotherapeutic approaches in HCC.http://www.ijpmonline.org/article.asp?issn=0377-4929;year=2011;volume=54;issue=3;spage=448;epage=453;aulast=ThakurCTLA-4FOXP3hepatocellular carcinomaimmuneregulationT-regulatory cells
spellingShingle Sapna Thakur
Anuj Singla
Yogesh Chawla
Arvind Rajwanshi
Naveen Kalra
Sunil K Arora
Expansion of peripheral and intratumoral regulatory T-cells in hepatocellular carcinoma: A case-control study
Indian Journal of Pathology and Microbiology
CTLA-4
FOXP3
hepatocellular carcinoma
immuneregulation
T-regulatory cells
title Expansion of peripheral and intratumoral regulatory T-cells in hepatocellular carcinoma: A case-control study
title_full Expansion of peripheral and intratumoral regulatory T-cells in hepatocellular carcinoma: A case-control study
title_fullStr Expansion of peripheral and intratumoral regulatory T-cells in hepatocellular carcinoma: A case-control study
title_full_unstemmed Expansion of peripheral and intratumoral regulatory T-cells in hepatocellular carcinoma: A case-control study
title_short Expansion of peripheral and intratumoral regulatory T-cells in hepatocellular carcinoma: A case-control study
title_sort expansion of peripheral and intratumoral regulatory t cells in hepatocellular carcinoma a case control study
topic CTLA-4
FOXP3
hepatocellular carcinoma
immuneregulation
T-regulatory cells
url http://www.ijpmonline.org/article.asp?issn=0377-4929;year=2011;volume=54;issue=3;spage=448;epage=453;aulast=Thakur
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