Dataset Information

Interaction between tumour-infiltrating B cells and T cells controls the progression of hepatocellular carcinoma.

ABSTRACT:

Objective

The nature of the tumour-infiltrating leucocytes (TILs) is known to impact clinical outcome in carcinomas, including hepatocellular carcinoma (HCC). However, the role of tumour-infiltrating B cells (TIBs) remains controversial. Here, we investigate the impact of TIBs and their interaction with T cells on HCC patient prognosis.

Design

Tissue samples were obtained from 112 patients with HCC from Singapore, Hong Kong and Zurich and analysed using immunohistochemistry and immunofluorescence. RNA expression of CD19, CD8A, IFNG was analysed using quantitative PCR. The phenotype of freshly isolated TILs was analysed using flow cytometry. A mouse model depleted of mature B cells was used for functional study.

Results

Tumour-infiltrating T cells and B cells were observed in close contact with each other and their densities are correlated with superior survival in patients with HCC. Furthermore, the density of TIBs was correlated with an enhanced expression of granzyme B and IFN-?, as well as with reduced tumour viability defined by low expression of Ki-67, and an enhanced expression of activated caspase-3 on tumour cells. CD27 and CD40 costimulatory molecules and TILs expressing activation marker CD38 in the tumour were also correlated with patient survival. Mice depleted of mature B cells and transplanted with murine hepatoma cells showed reduced tumour control and decreased local T cell activation, further indicating the important role of B cells.

Conclusions

The close proximity of tumour-infiltrating T cells and B cells indicates a functional interaction between them that is linked to an enhanced local immune activation and contributes to better prognosis for patients with HCC.

SUBMITTER: Garnelo M

PROVIDER: S-EPMC5284473 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Publications

Interaction between tumour-infiltrating B cells and T cells controls the progression of hepatocellular carcinoma.

Garnelo Marta M Tan Alex A Her Zhisheng Z Yeong Joe J Lim Chun Jye CJ Chen Jinmiao J Lim Kiat Hon KH Weber Achim A Chow Pierce P Chung Alexander A Ooi London Lucien Pj LL Toh Han Chong HC Heikenwalder Mathias M Ng Irene O L IO Nardin Alessandra A Chen Qingfeng Q Abastado Jean-Pierre JP Chew Valerie V

Gut 20151215 2

<h4>Objective</h4>The nature of the tumour-infiltrating leucocytes (TILs) is known to impact clinical outcome in carcinomas, including hepatocellular carcinoma (HCC). However, the role of tumour-infiltrating B cells (TIBs) remains controversial. Here, we investigate the impact of TIBs and their interaction with T cells on HCC patient prognosis.<h4>Design</h4>Tissue samples were obtained from 112 patients with HCC from Singapore, Hong Kong and Zurich and analysed using immunohistochemistry and im ...[more]

PMID: 26669617

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Project description:Gene expression profiles have been frequently integrated with the human protein interactome to uncover functional modules under specific conditions like disease state. Beyond traditional differential expression analysis, differential co-expression analysis has emerged as a robust approach to reveal condition-specific network modules, with successful applications in a few human disease studies. Hepatocellular carcinoma (HCC), which is often interrelated with the Hepatitis C virus, typically develops through multiple stages. A comprehensive investigation of HCC progression-specific differential co-expression modules may advance our understanding of HCC's pathophysiological mechanisms.Compared with differentially expressed genes, differentially co-expressed genes were found more likely enriched with Hepatitis C virus binding proteins and cancer-mutated genes, and they were clustered more densely in the human reference protein interaction network. These observations indicated that a differential co-expression approach could outperform the standard differential expression network analysis in searching for disease-related modules. We then proposed a differential co-expression network approach to uncover network modules involved in HCC development. Specifically, we discovered subnetworks that enriched differentially co-expressed gene pairs in each HCC transition stage, and further resolved modules with coherent co-expression change patterns over all HCC developmental stages. Our identified network modules were enriched with HCC-related genes and implicated in cancer-related biological functions. In particular, APC and YWHAZ were highlighted as two most remarkable genes in the network modules, and their dynamic interaction partnership was resolved in HCC development.We demonstrated that integration of differential co-expression with the protein interactome could outperform the traditional differential expression approach in discovering network modules of human diseases. In our application of this approach to HCC's gene expression data, we successfully identified subnetworks with marked differential co-expression in individual HCC stage transitions and network modules with coherent co-expression change patterns over all HCC developmental stages. Our results shed light on subtle HCC mechanisms, including temporal activation and dismissal of pivotal functions and dynamic interaction partnerships of key genes.

Dataset Information

Interaction between tumour-infiltrating B cells and T cells controls the progression of hepatocellular carcinoma.

Objective

Design

Results

Conclusions

Publications

Interaction between tumour-infiltrating B cells and T cells controls the progression of hepatocellular carcinoma.

Similar Datasets

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