scholarly journals COSTIMULATORY MOLECULE OX40, TUMOR IMMUNE MICROENVIRONMENT AND RESPONSE TO IMMUNOCHEMOTHERAPY IN DIFFUSE LARGE B‐CELL LYMPHOMA: AN INTEGRATIVE ANALYSIS WITH MOLECULAR CHARACTERISTICS

2021 ◽  
Vol 39 (S2) ◽  
Author(s):  
X Wang ◽  
Y Hong ◽  
Y Li ◽  
Q Guan ◽  
S Zhou ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Costimulatory Molecule ◽  
B Cell Lymphoma ◽  
Integrative Analysis ◽  
Molecular Characteristics ◽  
Immune Microenvironment ◽  
Large B Cell Lymphoma ◽  
Tumor Immune Microenvironment ◽  
Large B Cell

scholarly journals Tumor Immune Microenvironment Components and Checkpoint Molecules in Anaplastic Variant of Diffuse Large B-Cell Lymphoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Tianqi Xu ◽  
Jia Chai ◽  
Kaijing Wang ◽  
Qingge Jia ◽  
Yixiong Liu ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Genetic Alterations ◽  
Clinicopathological Features ◽  
Immune Microenvironment ◽  
Large B Cell Lymphoma ◽  
Tumor Immune Microenvironment ◽  
Large B Cell

BackgroundAnaplastic diffuse large B-cell lymphoma(A-DLBCL) is a rare morphological subtype characterized by the presence of polygonal, bizarre-shaped tumor cells. Our previous research found that A-DLBCL displays many genetic alterations and biological features that differ greatly from those of ordinary DLBCL. However, the status of tumor immune microenvironment components and checkpoint molecules in A-DLBCL remains unclear.MethodsThirty A-DLBCL patients were enrolled to study tumor immune microenvironment components and checkpoint molecules and their associations with clinicopathological features and prognosis.ResultsPatients with A-DLBCL presented higher expression of PD-L1 (40% vs 10%, P=0.004) than patients with ordinary DLBCL. FISH analysis showed that extra copies of PD-L1 were more frequent in A-DLBCL cases than in ordinary DLBCL cases (23.3% vs 4.0%, P=0.001). The numbers of PD-1+ TILs (tumor infiltrating lymphocytes) and CD8+T cells were significantly lower in A-DLBCL versus ordinary DLBCL. In contrast, the numbers of GATA3+ Th2 cells, FOXP3+ Tregs and CD33+ myeloid-derived suppressor cells (MDSCs) were significantly higher in A-DLBCL than in ordinary DLBCL. The associations between clinicopathological features and tumor immune microenvironment cell frequency were analyzed in A-DLBCL patients. Briefly, the number of PD-1+ TILs was lower and the number of CD33+ MDSCs was higher in patients with mutated TP53 compared to those with wild-type TP53. The number of FOXP3+ Tregs was much lower in patients with a noncomplete response (CR) to chemotherapy than in those with a complete response. The number of CD8+ T cells showed a decreasing trend in patients with high International Prognostic Index (IPI) scores and in those with concurrent MYC and BCL2 and/or BCL6 abnormalities. Univariate survival analysis showed that patients with PD-L1+, mPD-L1+(PD-L1+ nonmalignant stromal cells) or mPD-L1+ status had a significantly poorer overall survival (OS) than those with PD-L1- status. An increase in the number of CD3+ T cells, FOXP3+ Treg cells and T-bet+ Th1 cells was significantly associated with prolonged OS in patients with A-DLBCL.ConclusionOur study suggests that A-DLBCL displays a distinct pattern of tumor immune microenvironment components and checkpoint molecules that distinguish it from ordinary DLBCL. The analysis of tumor immune microenvironment components and checkpoint molecules could help in predicting the prognosis of A-DLBCL patients and determining therapeutic strategies targeting the tumor immune microenvironment.

scholarly journals Helicobacter pylori infection disturbs the tumor immune microenvironment and is associated with a discrepant prognosis in gastric de novo diffuse large B-cell lymphoma

2021 ◽  
Vol 9 (10) ◽  
pp. e002947
Author(s):  
Yuwei Deng ◽  
Wenjia Su ◽  
Junwen Zhu ◽  
Hongfei Ji ◽  
Xiaoping Zhou ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
B Cell ◽  
De Novo ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Immune Microenvironment ◽  
Large B Cell Lymphoma ◽  
Tumor Immune Microenvironment ◽  
H Pylori ◽  
Large B Cell

BackgroundGastric diffuse large B-cell lymphoma (gDLBCL) related to Helicobacter pylori infection exhibits a wide spectrum of prognosis, and the tumor immune microenvironment (TIME) affects tumor progression. However, there are few studies on the correlation between prognosis and changes of TIME induced by H. pylori infection in de novo gDLBCL.MethodsA retrospective study was performed to determine the prognostic value of TIME related to H. pylori infection in de novo gDLBCL. A total of 252 patients were included and have been treated with standard rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy or other similar regimens in addition to H. pylori eradication (HPE). All patients were stratified by H. pylori infection, HPE efficacy, and preliminary TIME evaluation using conventional criteria. Statistical analyses were conducted. To assess the mechanism, 30 subjects were assessed for H. pylori infection. The components and spatial distributions of TIME were analyzed.ResultsThe median follow-up of the 252 patients was 66.6 months (range 0.7–119.2), and the 5-year overall survival (OS) was 78.0%. A total of 109 H. pylori-positive cases with pathological complete remission and high tumor-infiltrating T lymphocytes (cohort 1) had significantly higher 5-year progression-free survival (88.1% vs 70.5%, p<0.001) and OS (89.2% vs 76.6%, p<0.001) than the other 143 patients (cohort 2). Among 30 patients, 19 were cytotoxin-associated gene A-marked as the cohort 1 subset. Compared with cohort 2, cohort 1 exhibited increased inflammatory factors (tumor necrosis factor-α, interferon γ, etc) and decreased immunosuppressive components (PD-L1, PD-1, IL-10, etc). There was reduced NF-kB activation. Cancer-promoting immune cells (PD-1hiTim-3+ CTL, Tregs, M2-like macrophages, etc) occupied a minor spatial distribution, while the antitumor subtypes increased, corresponding to favorable survival.ConclusionH. pylori-evoked inflammatory responses disturb the TIME, causing a differential prognosis in de novo gDLBCL, which can be used to identify patients who could benefit from HPE and immunochemotherapy.

Abstract 4490: Molecular characteristics of diffuse large B-cell lymphoma in HIV-positive and HIV-negative patients

2012 ◽  
Author(s):  
Clara J. Kim ◽  
Wendy Cozen ◽  
Lawrence M. Weiss ◽  
Kishor Bhatia ◽  
Myles Cockburn ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Hiv Positive ◽  
Molecular Characteristics ◽  
Large B Cell Lymphoma ◽  
Large B Cell ◽  
Hiv Negative

scholarly journals Integrative Analysis Reveals an Outcome-Associated and Targetable Pattern of p53 and Cell Cycle Deregulation in Diffuse Large B Cell Lymphoma

Cancer Cell ◽  
2012 ◽  
Vol 22 (3) ◽  
pp. 359-372 ◽  
Author(s):  
Stefano Monti ◽  
Bjoern Chapuy ◽  
Kunihiko Takeyama ◽  
Scott J. Rodig ◽  
Yansheng Hao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Integrative Analysis ◽  
Large B Cell Lymphoma ◽  
Cell Cycle Deregulation ◽  
Large B Cell

The molecular pathogenesis of primary mediastinal large B-cell lymphoma

Blood ◽  
2011 ◽  
Vol 118 (10) ◽  
pp. 2659-2669 ◽  
Author(s):  
Christian Steidl ◽  
Randy D. Gascoyne
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Immune Escape ◽  
Cell Lymphoma ◽  
Treatment Strategies ◽  
B Cell Lymphoma ◽  
Janus Kinase ◽  
Molecular Characteristics ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Primary mediastinal large B-cell lymphoma (PMBCL) is a recognized non-Hodgkin lymphoma entity with unique pathologic, clinical, and molecular characteristics distinct from those of other diffuse large B-cell lymphomas. Immunohistochemical characterization and molecular studies strongly suggest that PMBCL is of germinal center or postgerminal center origin. Pivotal gene expression profiling work defined major deregulated pathway activities that overlap with Hodgkin lymphoma and prompted a more detailed analysis of candidate genes. In particular, the nuclear factor-κB and the Janus Kinase-Signal Transducer and Activator of Transcription signaling pathways are targeted by multiple genomic hits, and constitutive activity of both pathways can be considered molecular hallmark alterations of PMBCL. Moreover, data are emerging giving unique insight into remodeling of the epigenome that affects transcriptional regulation of a multitude of genes. More recently, the tumor microenvironment of PMBCL has shifted into focus based on a number of gene perturbations altering expression of surface molecules that contribute to immune escape. These findings highlight the importance of immune privilege in the pathogenesis of PMBCL and suggest that disrupting crosstalk between the tumor cells and the microenvironment might be a rational new therapeutic target in conjunction with traditional treatment strategies.

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