Carreras, Joaquim;
Kikuti, Yara Yukie;
Hiraiwa, Shinichiro;
Miyaoka, Masashi;
Tomita, Sakura;
Ikoma, Haruka;
Ito, Atsushi;
... Nakamura, Naoya; + view all
(2021)
High PTX3 expression is associated with a poor prognosis in diffuse large B-cell lymphoma.
Cancer Science
, 113
(1)
pp. 334-348.
10.1111/cas.15179.
Preview |
Text
High PTX3 expression is associated with a poor prognosis in diffuse large B-cell lymphoma.pdf - Published Version Download (2MB) | Preview |
Abstract
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.
| Type: | Article |
|---|---|
| Title: | High PTX3 expression is associated with a poor prognosis in diffuse large B-cell lymphoma |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/cas.15179 |
| Publisher version: | https://doi.org/10.1111/cas.15179 |
| Language: | English |
| Additional information: | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Oncology, diffuse large B-cell lymphoma, IL-10, PD-L1, CD163, PTX3, TUMOR-ASSOCIATED MACROPHAGES, FOLLICULAR LYMPHOMA, GENE-EXPRESSION, HIGH NUMBERS, T-CELLS, SURVIVAL, LYMPHOCYTES, ACTIVATION, ENRICHMENT, BIOMARKERS |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10148932 |
Archive Staff Only
 |
View Item |
