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.
Highlights
Peripheral T cell lymphoma (PTCL), which is common in Asia [1], is an aggressive form of lymphoma associated with poor patient outcomes
We examined the prognostic value of two T-cell-specific transcription factors, GATA-binding protein 3 (GATA3) and T-bet, in PTCL, uncovered the pathogenesis of PTCL, and investigated new PTCL therapeutic targets
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
Summary
Peripheral T cell lymphoma (PTCL), which is common in Asia [1], is an aggressive form of lymphoma associated with poor patient outcomes. Clinical hematologists have widely adopted the 2010 World Health Organization (WHO) criteria to classify PTCLs into various subtypes, with PTCL-not otherwise specified (PTCL-NOS) being the most common [2, 3]. PTCL-NOS is an exclusive diagnosis comprised of PTCL cases not classifiable as any defined T-cell lymphoma entity. The normal cellular components of PTCL-NOS have not been accurately identified, and the immunophenotypic profiles of PTCL-NOS are heterogeneous [4]. There is no consolidated chemotherapy regimen for PTCL-NOS, and patient survival rates are less than 30%. There is an urgent need to further improve PTCL classification and develop targeted therapies based on the signaling pathways that are aberrantly expressed in PTCL subtypes
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