Prognostic relevance of CD4+ T-cells in the microenvironment of newly diagnosed follicular lymphoma (FL) patients is independent of the tumor gene expression profile.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8052-8052
Author(s):  
Patrizia Mondello ◽  
Angelo Fama ◽  
Melissa C. Larson ◽  
Andew L. Feldman ◽  
Zhi-Zhang J Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
High Risk ◽  
Follicular Lymphoma ◽  
Prognostic Score ◽  
Cd4 T Cell ◽  
Newly Diagnosed ◽  
Early Failure ◽  
Tumor Gene Expression ◽  
Tumor Gene

8052 Background: A significant proportion of patients with FL experience an early relapse and a subsequent poor outcome. While several prognostic indices have been developed, none were designed to predict early failure. Recently, we established that lack of intrafollicular CD4+ T-cell expression predicted risk of early failure, and integrating this microenvironment biomarker with the Follicular Lymphoma International Prognostic Index, termed BioFLIPI, further improved identification of FL patients at risk of early failure ( Blood 2019;134(suppl1):121). However, the microenvironment may be influenced by the genetic composition of tumor. We investigated whether the CD4 biomarker and BioFLIPI were impacted by genetic features of the tumor as assessed by a 23-gene expression prognostic score ( Lancet Oncol 2018;19:549-61). Methods: Of the 186 cases with FL grade 1-3A treated with immunochemotherapy (IC) in our prior study, 152 had digital expression quantification of 23 selected genes (23-GEP score), which used RNA from formalin-fixed, paraffin-embedded samples. Event-free survival (EFS) was defined as time from diagnosis to progression, relapse, retreatment, or death. Early failure was defined as failing to achieve EFS at 24 months. Risk of early failure was estimated using odds ratios (ORs) and 95% confidence intervals from logistic regression models. We also used Cox regression to assess associations with continuous EFS and overall survival (OS). Results: 28% of patients failed to achieve EFS24. Lack of CD4+ intrafollicular expression (38% of patients, OR = 2.33, p = 0.024) and high risk 23-GEP score (26% of patients, OR = 3.52, p = 0.001) each predicted early failure, and in a multivariable model that included FLIPI, both CD4+ (OR = 2.26, p = 0.046) and 23-GEP score (OR = 2.26, p = 0.0.057) remained predictors. Similarly, BioFLIPI modeled as a continuous score (1-4, OR per one point increase = 2.31, p < 0.001) predicted early failure, and the association remained (OR = 2.14, p < 0.001) when the high risk 23-GEP score (OR = 2.79, p = 0.013) was included in the model. When stratified on 23-GEP score, BioFLIPI was a stronger predictor of early failure in low risk (74%, OR = 2.51, p = 0.002) relative to high risk (26%, OR = 1.55, p = 0.27) patients. Similar patterns were observed for EFS and OS. Conclusions: CD4+ T-cell infiltrate and tumor gene expression appear to be independently predictive of early failure in newly diagnosed FL patients treated with IC. Future studies should integrate and validate these measures.

scholarly journals Lack of intrafollicular memory CD4 + T cells is predictive of early clinical failure in newly diagnosed follicular lymphoma

2021 ◽  
Vol 11 (7) ◽  
Author(s):  
Patrizia Mondello ◽  
Angelo Fama ◽  
Melissa C. Larson ◽  
Andrew L. Feldman ◽  
Jose C. Villasboas ◽  
...  
Keyword(s):  
T Cells ◽  
High Risk ◽  
Follicular Lymphoma ◽  
Cd4 T Cells ◽  
Risk Model ◽  
Risk Group ◽  
Tissue Microarrays ◽  
High Risk Group ◽  
Newly Diagnosed ◽  
Early Failure

AbstractDespite a characteristic indolent course, a substantial subset of follicular lymphoma (FL) patients has an early relapse with a poor outcome. Cells in the microenvironment may be a key contributor to treatment failure. We used a discovery and validation study design to identify microenvironmental determinants of early failure and then integrated these results into the FLIPI. In total, 496 newly diagnosed FL grade 1–3 A patients who were prospectively enrolled into the MER cohort from 2002 to 2012 were evaluated. Tissue microarrays were stained for CD4, CD8, FOXP3, CD32b, CD14, CD68, CD70, SIRP-α, TIM3, PD-1, and PD-L1. Early failure was defined as failing to achieve event-free survival at 24 months (EFS24) in immunochemotherapy-treated patients and EFS12 in all others. CyTOF and CODEX analysis were performed to characterize intratumoral immunophenotypes. Lack of intrafollicular CD4 expression was the only predictor of early failure that replicated with a pooled OR 2.37 (95%CI 1.48–3.79). We next developed a bio-clinical risk model (BioFLIPI), where lack of CD4 intrafollicular expression moved patients up one FLIPI risk group, adding a new fourth high-risk group. Compared with BioFLIPI score of 1, patients with a score of 2 (OR 2.17; 95% CI 1.08–4.69), 3 (OR 3.53; 95% CI 1.78–7.54), and 4 (OR 8.92; 95% CI 4.00–21.1) had increasing risk of early failure. The favorable intrafollicular CD4 T cells were identified as activated central memory T cells, whose prognostic value was independent from genetic features. In conclusion, lack of intrafollicular CD4 expression predicts early failure in FL and combined with FLIPI improves identification of high-risk patients; however, independent validation is warranted.

Low absolute CD4+ T cell counts in peripheral blood predict poor prognosis in patients with newly diagnosed multiple myeloma

2020 ◽  
Vol 61 (8) ◽  
pp. 1869-1876 ◽  
Author(s):  
Yan Gu ◽  
Yuanyuan Jin ◽  
Jie Ding ◽  
Wu Yujie ◽  
Qinglin Shi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cell ◽  
Peripheral Blood ◽  
Poor Prognosis ◽  
Cd4 T Cell ◽  
Newly Diagnosed ◽  
Cell Counts

scholarly journals Discordance in CD4+T-Cell Levels and Viral Loads with Co-Occurrence of Elevated Peripheral TNF-α and IL-4 in Newly Diagnosed HIV-TB Co-Infected Cases

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e70250 ◽  
Author(s):  
Ronald Benjamin ◽  
Atoshi Banerjee ◽  
Sharada Ramaseri Sunder ◽  
Sumanlatha Gaddam ◽  
Vijaya Lakshmi Valluri ◽  
...  
Keyword(s):  
T Cell ◽  
Cd4 T Cell ◽  
Newly Diagnosed ◽  
Viral Loads ◽  
Tnf Α

Resolving driver events in MLL-r negative high-risk infant ALL.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10030-10030
Author(s):  
Jennifer Seelisch ◽  
Matthew Zatzman ◽  
Federico Comitani ◽  
Fabio Fuligni ◽  
Ledia Brunga ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
High Risk ◽  
B Cell ◽  
Gene Expression Profiling ◽  
Rna Sequencing ◽  
Clinical Features ◽  
Expression Profiling ◽  
High Risk Infant ◽  
Childhood All

10030 Background: Infant acute lymphoblastic leukemia (ALL) is the only subtype of childhood ALL whose outcome has not improved over the past two decades. The most important prognosticator is the presence of rearrangements in the Mixed Lineage Leukemia gene (MLL-r), however, many patients present with high-risk clinical features but without MLL-r. We recently identified two cases of infant ALL with high-risk clinical features resembling MLL-r, but were negative for MLL-r by conventional diagnostics. RNA sequencing revealed a partial tandem duplication in MLL (MLL-PTD). We thus aimed to determine if MLL-PTD, other MLL abnormalities, or other genetic or transcriptomic features were driving this subset of high-risk infant ALL without MLL-r. Methods: We obtained 19 banked patient samples from the Children’s Oncology Group (COG) infant ALL trial (AALL0631) from MLL wildtype patients as determined by FISH and cytogenetics. Utilizing deep RNA-sequencing, we manually inspected the MLL gene for MLL-PTD, while also performing automated fusion detection and gene expression profiling in search of defining features of these tumors. Results: 3 additional MLL-PTDs were identified, all in patients with infant T-cell ALL, whereas both index cases were in patients with infant B-cell ALL. Gene expression profiling analysis revealed that all five MLL-PTD infants clustered together. Eight infants (7 with B-cell ALL) were found to have Ph-like expression. Five of these 8 infants were also found to have an IKZF1/JAK2 expression profile; one of these five had a PAX5-JAK2 fusion detected. Two infants (including the one noted above) had novel PAX5 fusions, known drivers of B-cell leukemia. Additional detected fusions included TCF3-PBX1 and TCF4-ZNF384. Conclusions: MLL-PTDs were found in both B- and T-cell infant ALL. Though Ph-like ALL has been described in adolescents and young adults, we found a substantial frequency of Ph-like expression among MLL-WT infants. Further characterization of these infants is ongoing. If replicated in other infant cohorts, these two findings may help explain the poor prognosis of MLL-WT ALL when compared to children with standard risk ALL, and offer the possibility of targeted therapy for select infants.

Dual Hypergraph Regularized PCA for Biclustering of Tumor Gene Expression Data

2019 ◽  
Vol 31 (12) ◽  
pp. 2292-2303 ◽  
Author(s):  
Xuesong Wang ◽  
Jian Liu ◽  
Yuhu Cheng ◽  
Aiping Liu ◽  
Enhong Chen
Keyword(s):  
Gene Expression ◽  
Gene Expression Data ◽  
Expression Data ◽  
Tumor Gene Expression ◽  
Tumor Gene

scholarly journals Clinicopathological significance and prognostic value of Wilms' tumor gene expression in colorectal cancer

2015 ◽  
Vol 15 (6) ◽  
pp. 789-797 ◽  
Author(s):  
Yukinaga Miyata ◽  
Kenichi Kumagai ◽  
Tomoko Nagaoka ◽  
Kazutaka Kitaura ◽  
Goro Kaneda ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Prognostic Value ◽  
Wilms Tumor ◽  
Wilms Tumor Gene ◽  
Clinicopathological Significance ◽  
Tumor Gene Expression ◽  
Tumor Gene

scholarly journals S100 TREATMENT-DEPENDENCE OF HIGH-RISK GENE EXPRESSION SIGNATURES IN DE NOVO FOLLICULAR LYMPHOMA

HemaSphere ◽  
2019 ◽  
Vol 3 (S1) ◽  
pp. 1
Author(s):  
C. Bolen ◽  
W. Hiddemann ◽  
R. Marcus ◽  
M. Herold ◽  
S. Huet ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Risk ◽  
Follicular Lymphoma ◽  
De Novo ◽  
Risk Gene ◽  
Gene Expression Signatures

scholarly journals Simultaneous enumeration of cancer and immune cell types from bulk tumor gene expression data

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Julien Racle ◽  
Kaat de Jonge ◽  
Petra Baumgaertner ◽  
Daniel E Speiser ◽  
David Gfeller
Keyword(s):  
Gene Expression ◽  
Gene Expression Data ◽  
Immune Cell ◽  
Expression Profiles ◽  
Cell Types ◽  
Response To Therapy ◽  
Expression Data ◽  
Cell Type ◽  
Tumor Gene Expression ◽  
Tumor Gene

Immune cells infiltrating tumors can have important impact on tumor progression and response to therapy. We present an efficient algorithm to simultaneously estimate the fraction of cancer and immune cell types from bulk tumor gene expression data. Our method integrates novel gene expression profiles from each major non-malignant cell type found in tumors, renormalization based on cell-type-specific mRNA content, and the ability to consider uncharacterized and possibly highly variable cell types. Feasibility is demonstrated by validation with flow cytometry, immunohistochemistry and single-cell RNA-Seq analyses of human melanoma and colorectal tumor specimens. Altogether, our work not only improves accuracy but also broadens the scope of absolute cell fraction predictions from tumor gene expression data, and provides a unique novel experimental benchmark for immunogenomics analyses in cancer research (http://epic.gfellerlab.org).

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