Intratumoral regulatory T cells with higher prevalence and more suppressive activity in hepatocellular carcinoma patients
| Autor: | Pei Chen, Han Wu, Shuang-Jian Qiu, Jia Fan, Xiao-Yan Cai, Yong Yi, Jian Sun, Jia-Xing Wang, Jian-Jun Jin, Hong-Wei He, Yun-Feng Cheng, Rui Liao, Yi-Wei Li |
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| Rok vydání: | 2013 |
| Předmět: |
Hepatology
Regulatory T cell Microarray analysis techniques medicine.medical_treatment Gastroenterology hemic and immune systems chemical and pharmacologic phenomena Immunotherapy Biology Immune tolerance Gene expression profiling medicine.anatomical_structure Immunology medicine IL-2 receptor CD154 Interleukin-7 receptor |
| Zdroj: | Journal of Gastroenterology and Hepatology. 28:1555-1564 |
| ISSN: | 0815-9319 |
| DOI: | 10.1111/jgh.12202 |
| Popis: | Background and Aim: Regulatory T cells (Treg) play a vital role in immunosuppressive crosstalk; however, Tregs from different locations lead to different clinical outcomes. Our aim was, therefore, to compare the prevalences and suppressive phenotypes of Tregs in the peripheral blood, peritumor, and intratumor of patients with hepatocellular carcinoma (HCC). Methods: The frequencies and phenotypes of CD4 + CD25 + CD127 low/- CD49d - Tregs in the periphery, peritumor, and intratumor of 78 HCC patients and 12 healthy controls were evaluated by flow cytometry. Treg-cell suppressive activity was determined using an in vitro CD154 expression assay. Tregs from tumor and paired peritumor were then hybrid- ized using an Agilent whole genome oligo microarray, and selected genes were validated by real-time polymerase chain reaction. Functional analysis of the microarray data was performed using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses. Results: Intratumoral Tregs exhibited higher frequencies and more suppressive pheno- typic functions than those in peritumor and periphery, whereas there was no difference between the latter two. Functional analysis showed that complement cascades, p53, and glycosylphosphatidylinositol-anchor biosynthesis pathways were significantly upregulated in intratumoral Tregs; the salivary secretion pathway was significantly downregulated in intratumoral Tregs, and immune cells and tumor-immuno-related Gene Ontology terms were significantly affected. Conclusions: Tregs in different locations exhibited different functional statuses. A higher prevalence and more suppressive phenotype suggested a critical role for intratumoral Tregs in the formation of multicellular immunosuppressive networks. HCC immunotherapy may be improved, therefore, by specific locational Tregs elimination or suppression. |
| Databáze: | OpenAIRE |
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