title: GATA3 expression correlates with poor prognosis and tumor-associated macrophage infiltration in peripheral T cell lymphoma.
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.
authors: Department of Hematology, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences and PUMC, Beijing, 100730, China.
authors: Wei
authors: W
authors: Zhang
authors: Department of Hematology, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences and PUMC, Beijing, 100730, China.
authors: Zi
authors: Z
authors: Wang
authors: Department of Immunology, Institute of Basic Medical Science, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China.
authors: Yunping
authors: Y
authors: Luo
authors: Department of Pathology, PUMC Hospital, Chinese Academy of Medical Sciences and PUMC, Beijing, 100730, China.
authors: Dingrong
authors: D
authors: Zhong
authors: Department of Pathology, PUMC Hospital, Chinese Academy of Medical Sciences and PUMC, Beijing, 100730, China.
authors: Yufeng
authors: Y
authors: Luo
authors: Department of Hematology, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences and PUMC, Beijing, 100730, China.
authors: Daobin
authors: D
authors: Zhou
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002454:Cell Differentiation / Q000276:immunology; D005260:Female; D050990:GATA3 Transcription Factor / Q000096:biosynthesis*; D006801:Humans; D053208:Kaplan-Meier Estimate; D016411:Lymphoma, T-Cell, Peripheral / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human
keywords: GATA3; Hut78; T-bet; peripheral T-cell lymphoma; tumor-associated macrophages