2026-04-30T10:04:04Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/189292024-11-29T18:43:10Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Carreras, Joaquim
author
Kikuti, Yara Yukie
author
Hiraiwa, Shinichiro
author
Miyaoka, Masashi
author
Tomita, Sakura
author
Ikoma, Haruka
author
Ito, Atsushi
author
Kondo, Yusuke
author
Itoh, Johbu
author
Roncador, Giovanna
author
Martinez, Antonio
author
Colomo, Lluis
author
Hamoudi, Rifat
author
Ando, Kiyoshi
author
Nakamura, Naoya
funder
Ministry of Education, Culture, Sports, Science, and Technology (Japón)
funder
University of Tokyo (Japón)
funder
Al Jalila Foundation
funder
Sharjah Research Academy
funder
University of Sharjah (Emiratos Árabes Unidos)
funder
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (KAKENHI)
2024-03-13T12:42:35Z
2024-03-13T12:42:35Z
2022-01
Cancer Sci . 2022 ;113(1):334-348
10.1111/cas.15179
1349-7006
Cancer science
34706126
http://hdl.handle.net/20.500.12105/18929
Tumor-associated macrophages (TAMs) are associated with a poor prognosis of diffuse large B-cell lymphoma (DLBCL). As macrophages are heterogeneous, the immune polarization and their pathological role warrant further study. We characterized the microenvironment of DLBCL by immunohistochemistry in a training set of 132 cases, which included 10 Epstein-Barr virus-encoded small RNA (EBER)-positive and five high-grade B-cell lymphomas, with gene expression profiling in a representative subset of 37 cases. Diffuse large B-cell lymphoma had a differential infiltration of TAMs. The high infiltration of CD68 (pan-macrophages), CD16 (M1-like), CD163, pentraxin 3 (PTX3), and interleukin (IL)-10-positive macrophages (M2c-like) and low infiltration of FOXP3-positive regulatory T lymphocytes (Tregs) correlated with poor survival. Activated B cell-like DLBCL was associated with high CD16, CD163, PTX3, and IL-10, and EBER-positive DLBCL with high CD163 and PTX3. Programmed cell death-ligand 1 positively correlated with CD16, CD163, IL-10, and RGS1. In a multivariate analysis of overall survival, PTX3 and International Prognostic Index were identified as the most relevant variables. The gene expression analysis showed upregulation of genes involved in innate and adaptive immune responses and macrophage and Toll-like receptor pathways in high PTX3 cases. The prognostic relevance of PTX3 was confirmed in a validation set of 159 cases. Finally, in a series from Europe and North America (GSE10846, R-CHOP-like treatment, n = 233) high gene expression of PTX3 correlated with poor survival, and moderately with CSF1R, CD16, MITF, CD163, MYC, and RGS1. Therefore, the high infiltration of M2c-like immune regulatory macrophages and low infiltration of FOXP3-positive Tregs is associated with a poor prognosis in DLBCL, for which PTX3 is a new prognostic biomarker.
eng
High PTX3 expression is associated with a poor prognosis in diffuse large B-cell lymphoma.
journal article
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HighPTX3expressionisassociated_2022.pdf.txt
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