GATA-3 expression identifies a high-risk subset of PTCL, NOS with distinct molecular and clinical features

Autor:	Thomas M. Lanigan, Thomas E. Witzig, Alexandra C. Hristov, Robert Briski, Linda Wellik, David A. Wada, Ye Lu, Mark R. Pittelkow, Tianjiao Wang, Ryan A. Wilcox, Megan S. Lim, Andrew L. Feldman, Thomas M. Habermann, Avery Polk, Nathanael G. Bailey, Dafydd G. Thomas, Kay M. Ristow, Steven C. Ziesmer, Stephen M. Ansell
Rok vydání:	2014
Předmět:	Tumor microenvironment Lymphoid Neoplasia T cell Lymphocyte Immunology Macrophage polarization Interleukin Cell Biology Hematology Biology medicine.disease Biochemistry Lymphoma Interleukin 10 medicine.anatomical_structure medicine STAT protein Cancer research
Zdroj:	Blood. 123:3007-3015
ISSN:	1528-0020 0006-4971
DOI:	10.1182/blood-2013-12-544809
Popis:	The cell of origin and the tumor microenvironment’s role remain elusive for the most common peripheral T-cell lymphomas (PTCLs). As macrophages promote the growth and survival of malignant T cells and are abundant constituents of the tumor microenvironment, their functional polarization was examined in T-cell lymphoproliferative disorders. Cytokines that are abundant within the tumor microenvironment, particularly interleukin (IL)-10, were observed to promote alternative macrophage polarization. Macrophage polarization was signal transducer and activator of transcription 3 dependent and was impaired by the Janus kinase inhibitor ruxolitinib. In conventional T cells, the production of T helper (Th)2-associated cytokines and IL-10, both of which promote alternative macrophage polarization, is regulated by the T-cell transcription factor GATA-binding protein 3 (GATA-3). Therefore, its role in the T-cell lymphomas was examined. GATA-3 expression was observed in 45% of PTCLs, not otherwise specified (PTCL, NOS) and was associated with distinct molecular features, including the production of Th2-associated cytokines. In addition, GATA-3 expression identified a subset of PTCL, NOS with distinct clinical features, including inferior progression-free and overall survival. Collectively, these data suggest that further understanding the cell of origin and lymphocyte ontogeny among the T-cell lymphomas may improve our understanding of the tumor microenvironment’s pathogenic role in these aggressive lymphomas.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6813b7f55072a1a69b9571a820de893c https://doi.org/10.1182/blood-2013-12-544809 Zobrazit plný text záznamu