2026-04-30T10:04:03Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/189292024-11-29T18:43:10Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc 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 author 2022-01 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. Cancer Sci . 2022 ;113(1):334-348 10.1111/cas.15179 1349-7006 Cancer science 34706126 http://hdl.handle.net/20.500.12105/18929 High PTX3 expression is associated with a poor prognosis in diffuse large B-cell lymphoma.