Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/147837
Title: High TNFRSF14 and low BTLA are associated with poor prognosis in Follicular Lymphoma and in Diffuse Large B-cell Lymphoma transformation
Author: Carreras, Joaquim
López Guillermo, Armando
Kikuti, Yara Yukie
Itoh, Johbu
Masashi, Miyaoka
Ikoma, Haruka
Tomita, Sakura
Hiraiwa, Shinichiro
Hamoudi, Rifat
Rosenwald, Andreas
Leich, Ellen
Martínez, Antonio
Roncador, Giovanna
Villamor, Neus
Colomo Saperas, Lluís
Pérez Galán, Patricia
Tsuji, Noriko M.
Campo Güerri, Elias
Nakamura, Naoya
Keywords: Cèl·lules B
Limfomes
B cells
Lymphomas
Issue Date: 1-Jan-2019
Publisher: The Japanese Society for Lymphoreticular Tissue Research
Abstract: The microenvironment influences the behavior of follicular lymphoma (FL) but the specific roles of the immunomodulatory BTLA and TNFRSF14 (HVEM) are unknown. Therefore, we examined their immunohistochemical expression in the intrafollicular, interfollicular and total histological compartments in 106 FL cases (57M/49F; median age 57-years), and in nine relapsed-FL with transformation to DLBCL (tFL). BTLA expression pattern was of follicular T-helper cells (TFH) in the intrafollicular and of T-cells in the interfollicular compartments. The mantle zones were BTLA+ in 35.6% of the cases with similar distribution of IgD. TNFRSF14 expression pattern was of neoplastic B lymphocytes (centroblasts) and "tingible body macrophages". At diagnosis, the averages of total BTLA and TNFRSF14-positive cells were 19.2%±12.4STD (range, 0.6%-58.2%) and 46.7 cells/HPF (1-286.5), respectively. No differences were seen between low-grade vs. high-grade FL but tFL was characterized by low BTLA and high TNFRSF14 expression. High BTLA correlated with good overall survival (OS) (total-BTLA, Hazard Risk=0.479, P=0.022) and with high PD-1 and FOXP3+Tregs. High TNFRSF14 correlated with poor OS and progression-free survival (PFS) (total-TNFRSF14, HR=3.9 and 3.2, respectively, P<0.0001), with unfavorable clinical variables and higher risk of transformation (OR=5.3). Multivariate analysis including BTLA, TNFRSF14 and FLIPI showed that TNFRSF14 and FLIPI maintained prognostic value for OS and TNFRSF14 for PFS. In the GSE16131 FL series, high TNFRSF14 gene expression correlated with worse prognosis and GSEA showed that NFkB pathway was associated with the "High-TNFRSF14/dead-phenotype". In conclusion, the BTLA-TNFRSF14 immune modulation pathway seems to play a role in the pathobiology and prognosis of FL.
Note: Reproducció del document publicat a: https://doi.org/10.3960/jslrt.19003
It is part of: Journal of Clinical and Experimental Hematopathology, 2019, vol. 59, num. 1, p. 1-16
URI: http://hdl.handle.net/2445/147837
Related resource: https://doi.org/10.3960/jslrt.19003
ISSN: 1346-4280
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Fonaments Clínics)

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