PMID- 30918139
OWN - NLM
STAT- MEDLINE
DCOM- 20190419
LR  - 20200225
IS  - 1880-9952 (Electronic)
IS  - 1346-4280 (Print)
IS  - 1346-4280 (Linking)
VI  - 59
IP  - 1
DP  - 2019
TI  - High TNFRSF14 and low BTLA are associated with poor prognosis in Follicular 
      Lymphoma and in Diffuse Large B-cell Lymphoma transformation.
PG  - 1-16
LID - 10.3960/jslrt.19003 [doi]
AB  - 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.
FAU - Carreras, Joaquim
AU  - Carreras J
FAU - Lopez-Guillermo, Armando
AU  - Lopez-Guillermo A
FAU - Kikuti, Yara Yukie
AU  - Kikuti YY
FAU - Itoh, Johbu
AU  - Itoh J
FAU - Masashi, Miyaoka
AU  - Masashi M
FAU - Ikoma, Haruka
AU  - Ikoma H
FAU - Tomita, Sakura
AU  - Tomita S
FAU - Hiraiwa, Shinichiro
AU  - Hiraiwa S
FAU - Hamoudi, Rifat
AU  - Hamoudi R
FAU - Rosenwald, Andreas
AU  - Rosenwald A
FAU - Leich, Ellen
AU  - Leich E
FAU - Martinez, Antonio
AU  - Martinez A
FAU - Roncador, Giovanna
AU  - Roncador G
FAU - Villamor, Neus
AU  - Villamor N
FAU - Colomo, Lluis
AU  - Colomo L
FAU - Perez, Patricia
AU  - Perez P
FAU - Tsuji, Noriko M
AU  - Tsuji NM
FAU - Campo, Elias
AU  - Campo E
FAU - Nakamura, Naoya
AU  - Nakamura N
LA  - eng
PT  - Journal Article
PL  - Japan
TA  - J Clin Exp Hematop
JT  - Journal of clinical and experimental hematopathology : JCEH
JID - 101141257
RN  - 0 (BTLA protein, human)
RN  - 0 (Immunologic Factors)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Receptors, Tumor Necrosis Factor, Member 14)
RN  - 0 (TNFRSF14 protein, human)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - B-Lymphocytes/chemistry/pathology
MH  - Cell Transformation, Neoplastic
MH  - Female
MH  - Humans
MH  - Immunologic Factors
MH  - Lymphoma, Follicular/*diagnosis/mortality
MH  - Lymphoma, Large B-Cell, Diffuse/*diagnosis/mortality
MH  - Male
MH  - Middle Aged
MH  - Prognosis
MH  - Receptors, Immunologic/*metabolism
MH  - Receptors, Tumor Necrosis Factor, Member 14/*metabolism
MH  - Survival Analysis
MH  - T-Lymphocytes/chemistry
PMC - PMC6528140
OTO - NOTNLM
OT  - BTLA
OT  - Follicular lymphoma
OT  - TNFRSF14 (HVEM)
OT  - immune microenvironment
OT  - transformed follicular lymphoma
COIS- CONFLICT OF INTEREST: The authors have no conflict of interest to declare.
EDAT- 2019/03/29 06:00
MHDA- 2019/04/20 06:00
PMCR- 2019/03/27
CRDT- 2019/03/29 06:00
PHST- 2019/03/29 06:00 [entrez]
PHST- 2019/03/29 06:00 [pubmed]
PHST- 2019/04/20 06:00 [medline]
PHST- 2019/03/27 00:00 [pmc-release]
AID - 19003 [pii]
AID - 10.3960/jslrt.19003 [doi]
PST - ppublish
SO  - J Clin Exp Hematop. 2019;59(1):1-16. doi: 10.3960/jslrt.19003.