Increased Frequency of Foxp3+ Regulatory T Cells in Mice with Hepatocellular Carcinoma

Yong Du,Zhi-Ming Huang,Qing Niu,Xin Chen,Xiao-Hua Ye

doi:10.7314/apjcp.2012.13.8.3815

Abstract

The CD4+CD25+ regulatory T cell (Treg) is a special kind of T cell subset. Studies have showed that Treg cells are involved in a number of physiological processes and pathologic conditions such as autoimmune diseases, transplantation tolerance and cancer. Tregs with unique capacity for immune inhibition can impair anti-tumour immunity and help tumor cells to escape from immune surveillance. The aim of our study was to investigate whether Tregs are involved in hepatocellular carcinoma (HCC). A BABL/C mouse with HCC in situ model was established to evaluate the Treg existence in carcinoma tissues and the changes of Tregs in spleen using flow cytometry and immunohistochemistry methods. Granzyme B expression in carcinoma tissues was analyzed by immunohistochemistry to investigate the tumor local immune status. The proportion of CD4+CD25+/CD4+ spleen lymphocytes of tumor bearing mice (18.8% ± 1.26%) was found to be significantly higher than that in normal mice (9.99% ± 1.90%) (P<0.01 ). Immunohistochemistry of spleen tissue also confirmed that there was an increase in Treg in tumor-bearing mice, while in carcinomas it showed Treg cells to be present in tumor infiltrating lymphocyte areas while Granzyme B was rarely observed. Anti-tumour immunity was suppressed, and this might be associated with the increase of Tregs. Our observations suggest that the CD4+CD25+Treg/ CD4+ proportion in spleen lymphocytes can be a sensitive index to evaluate the change of Tregs in hepatocellular carcinoma mice and the Treg may be a promising therapeutic target for cancer.

Highlights

Hepatocellular carcinoma (HCC)is one of the leading causes of cancer related death in the world and about 60-70 ten thousands have died in this disease (Kudo et al, 2010)
Granzyme B expression in carcinoma tissues was analyzed by immunohistochemistry to investigate the tumor local immune status.The proportion of CD4+CD25+/CD4+ spleen lymphocytes of tumor bearing mice (18.8%±1.26%) was found to be significantly higher than that in normal mice (9.99%±1.90%) (P
Immunohistochemistry of spleen tissue confirmed that there was an increase in Treg in tumor-bearing mice, while in carcinomas it showed Treg cells to be present in tumor infiltrating lymphocyte areas while Granzyme B was rarely observed

Summary

Introduction

Hepatocellular carcinoma (HCC)is one of the leading causes of cancer related death in the world and about 60-70 ten thousands have died in this disease (Kudo et al, 2010). It has been shown that Tregs play a critical role in anti-tumour immune responses. Tregs with their unique immune inhibition can impair the anti-tumour immune and help tumor cells to escape from immune surveillance. Many researchs have found an increased number of Treg in various cancers, such as gastric carcinoma, pancreatic cancer, prostate cancer and breast carcinoma, etc (Miller et al, 2006; Nummer et al, 2007; Gupta et al, 2007; Ghebeh et al, 2008; Mizukami et al, 2008) and deletion of CD25+ cells may cause tumor regression (Onizuka et al, 1999; Shimizu et al, 1999). Studies have reported an increase in Treg population in both the peripheral blood and tumor microenvironment in HCC patients (Thakur et al, 2011), there are almost no researches that describe the change of Treg in spleens and the tumor local immune status

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