Oncotarget

Research Papers:

GATA3 expression correlates with poor prognosis and tumor-associated macrophage infiltration in peripheral T cell lymphoma

Wei Editor, Zi Wang, Yunping Luo, Dingrong Zhong, Yufeng Luo and Daobin Zhou _

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Oncotarget. 2016; 7:65284-65294. https://doi.org/10.18632/oncotarget.11673

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Abstract

Wei Zhang1,*, Zi Wang1,*, Yunping Luo2, Dingrong Zhong3, Yufeng Luo3, Daobin Zhou1

1Department of Hematology, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences and PUMC, Beijing, 100730, China

2Department of Immunology, Institute of Basic Medical Science, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China

3Department of Pathology, PUMC Hospital, Chinese Academy of Medical Sciences and PUMC, Beijing, 100730, China

*These authors have contributed equally to this work

Correspondence to:

Daobin Zhou, email: zhoudb@pumch.cn

Keywords: GATA3, T-bet, peripheral T-cell lymphoma, tumor-associated macrophages, Hut78

Received: May 01, 2016     Accepted: August 13, 2016     Published: August 29, 2016

ABSTRACT

Peripheral T cell lymphoma (PTCL) is an aggressive form of non-Hodgkin’s lymphoma characterized by a poor prognosis. In this study, we examined the prognostic value of two T-cell-specific transcription factors, GATA3 and T-bet, in PTCL, uncovered the pathogenesis of PTCL, and investigated new PTCL therapeutic targets. Samples from 109 PTCL patients were examined for expression of GATA3, T-bet and CD68. High GATA3 expression correlated with poor survival in PTCL patients and with tumor-associated macrophage (TAM) infiltration, as indicated by the presence of CD68-positive cells. Multivariate analysis further confirmed that high GATA3 expression and Eastern Cooperative Oncology Group (ECOG) scores higher than 2 were independent predictors of patient survival. Using lentiviral transfection to induce stable GATA3 knockdown in a PTCL cell line, we observed that GATA-3 knockdown in Hut78 cells decreased levels of IL4, IL5, IL13 and VEGF mRNA and reduced the number of co-cultured U937 cells that differentiated towards the M2 phenotype. These results suggest that high GATA3 expression is a predictor of a poor prognosis in PTCL, and that T lymphoma cells promote M2-type macrophage differentiation through a GATA3-dependent mechanism.


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