Journal of Clinical and Experimental Hematopathology
Online ISSN : 1880-9952
Print ISSN : 1346-4280
ISSN-L : 1346-4280
Original Article
High TNFRSF14 and low BTLA are associated with poor prognosis in Follicular Lymphoma and in Diffuse Large B-cell Lymphoma transformation
Joaquim CarrerasArmando Lopez-GuillermoYara Yukie KikutiJohbu ItohMiyaoka MasashiHaruka IkomaSakura TomitaShinichiro HiraiwaRifat HamoudiAndreas RosenwaldEllen LeichAntonio MartinezGiovanna RoncadorNeus VillamorLluis ColomoPatricia PerezNoriko M TsujiElias CampoNaoya Nakamura
Author information
JOURNALS FREE ACCESS

2019 Volume 59 Issue 1 Pages 1-16

Details
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.

Information related to the author
© 2019 by The Japanese Society for Lymphoreticular Tissue Research
Next article
feedback
Top