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.

A Retrospective Analysis of Gastric Diffuse Large B-Cell Lymphoma with or without MALT Component

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4856-4856
Author(s):  
Xiaowu Li ◽  
Bing Xia ◽  
Shanqi Guo ◽  
Eduardo M. Sotomayor ◽  
Yong Yu ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
B Cell ◽  
Clinical Characteristics ◽  
De Novo ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Advanced Stage ◽  
Large B Cell Lymphoma ◽  
H Pylori ◽  
Large B Cell

Abstract Abstract 4856 Background: The aim of this study was to evaluate the clinical characteristics, prognostic factors and survival outcomes of patients with gastric diffuse large B-cell lymphoma (DLBCL). Patients and methods: 162 patients with gastric DLBCL were evaluated retrospectively. Comparisons were made between patients of gastric DLBCL with component of mucosa-associated lymphoid tissue lymphoma (DLBCL/MALT) and patients of gastric DLBCL without detectable MALT component (de novo DLBCL). Results: Results according to the distribution of sex, age, stage, performance status, and other clinical characteristics were similar between de novo DLBCL group and DLBCL/MALT group (p>0.05). The ratio of patients with the germinal center B-cell-like (GCB) subtype to non-GCB subtype did not differ significantly between the two groups (1:1.1 versus 1:1.6, p=0.319). However, the proportion of patients with the stage-modified international prognostic index (m-IPI) ≥2 was higher in DLBCL/MALT groups (18%) than taht in de novo DLBCL groups (34%) (p=0.026). In addition, the H. pylori infection rate was 75% in DLBCL/MALT versus 38% in de novo DLBCL (p<0.001). Patients with de novo DLBCL have better 5-year PFS and OS estimates than those DLBCL/MALT patients (p=0.037 and 0.019 for the 5-year PFS and OS estimates, respectively). Surgical treatment did not offer survival benefit when compared with chemotherapy (p=0.405 and 0.065 for the 5-year PFS and OS estimates, respectively). Multivariate analysis revealed that non-GCB classification and m-IPI≥2 were independently associated with shorter OS and advanced stage was independently associated with shorter PFS. Conclusion: Gastric DLBCL is a heterogeneous disease that included de novo DLBCL and DLBCL/MALT lymphoma. Compared with the former, the latter has a higher H. pylori infection rate. And what's more, the proportion of patients with m-IPI≥2 is higher in DLBCL/MALT groups. De novo DLBCL was associated with higher 5-year PFS and OS estimates. Non-surgical treatment should be a primary consideration for gastric DLBCL. Immunophenotype classification and m-IPI were the most reliable factors for OS, and advanced stage was for PFS. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Progression of Primary Gastric Diffuse Large B-Cell Lymphoma after Helicobacter pylori Eradication

2020 ◽  
Vol 14 (3) ◽  
pp. 534-539
Author(s):  
Makoto Saito ◽  
Akio Mori ◽  
Reiki Ogasawara ◽  
Koh Izumiyama ◽  
Masanobu Morioka ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
B Cell ◽  
Cell Lymphoma ◽  
Treatment Strategies ◽  
B Cell Lymphoma ◽  
Endoscopic Biopsy ◽  
Chronic Active Gastritis ◽  
Large B Cell Lymphoma ◽  
H Pylori ◽  
Large B Cell

In <i>Helicobacter pylori</i>-positive, localized primary gastric diffuse large B-cell lymphoma (DLBCL), an increasing number of reports have recently been published on the effectiveness of <i>H. pylori</i> eradication (HPE). However, HPE treatment strategies for gastric DLBCL, including its indications, have yet to be examined. No detailed report has been published on a case of gastric DLBCL unsuccessfully treated by HPE. A 64-year-old female and a 70-year-old male were pathologically diagnosed with chronic active gastritis and mucosa-associated lymphoid tissue lymphoma, respectively. Both patients were positive for <i>H. pylori</i>, so HPE was employed. The disease progressed within 1 year, and both patients were pathologically diagnosed with DLBCL by endoscopic biopsy. On reviewing the first pathology slide, both patients were diagnosed with DLBCL. That is, the 2 patients had primary gastric DLBCL; however, they exhibited progressive disease after HPE. This failure of HPE treatment may be due to the initial lymphomas being multiplex ulcerative lesions. In both cases, complete remission was achieved by chemotherapy (plus radiation therapy) without recurrence for more than 3 years.

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.

De novo CD5-positive diffuse large B-cell lymphoma: clinical characteristics and therapeutic outcome

1999 ◽  
Vol 105 (4) ◽  
pp. 1133-1139 ◽  
Author(s):  
Motoko Yamaguchi ◽  
Toshiyuki Ohno ◽  
Kouji Oka ◽  
Masanori Taniguchi ◽  
Motohiro Ito ◽  
...  
Keyword(s):  
B Cell ◽  
Clinical Characteristics ◽  
De Novo ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Therapeutic Outcome ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals Clinical and prognostic significance of aberrant T-cell marker expression in 225 cases of de novo diffuse large B-cell lymphoma and 276 cases of other B-cell lymphomas

Oncotarget ◽  
2017 ◽  
Vol 8 (20) ◽  
pp. 33487-33500 ◽  
Author(s):  
Naoko Tsuyama ◽  
Daisuke Ennishi ◽  
Masahiro Yokoyama ◽  
Satoko Baba ◽  
Reimi Asaka ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
De Novo ◽  
Cell Lymphoma ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Cell Marker ◽  
Large B Cell Lymphoma ◽  
Marker Expression ◽  
Large B Cell

scholarly journals Prognostic significance of CXCR4 and mTOR expression in diffuse large B-cell lymphoma patients

2019 ◽  
Vol 9 (1) ◽  
pp. 7
Author(s):  
Rasha Haggag ◽  
Naglaa A. Mostafa ◽  
Marwa Nabil ◽  
Hala A. Shokralla ◽  
Neveen F. H. Sidhom
Keyword(s):  
B Cell ◽  
De Novo ◽  
Cell Lymphoma ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Poor Response ◽  
Cxcr4 Expression ◽  
Response To Treatment ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Background: The aim of this study was to investigate the prognostic role of mammalian target of Rapamycin (mTOR) and C-X-C chemokine receptor type 4 (CXCR4) in diffuse large-B-cell lymphoma (DLBCL) patients.Patients and methods: This retrospective study was collected data from 64 de novo DLBCL patients, who received standardized R-CHOP therapy at two oncology centers. CXCR4 and mTOR expressions were assessed by immunohistochemistry.Results: Out of the 64 DLBCL patients, 40 patients were positive for CXCR4 (62.5%) and 35 patients for mTOR (54.7%) expressions. CXCR4 expression was positively correlated with mTOR expression (r = 0.7; p < .001). While mTOR expression was significantly associated with high lactate dehydrogenase level (p = .03) and number of extranodal sites one or more (p =.02), CXCR4 expression was significantly associated with high IPI score (p < .001) and ECOG PS (p = .005). Furthermore, theexpression levels of mTOR and CXCR4 were significantly associated with older ages and poor response to treatment (p = .04, <.001 and .04, .03, respectively). After a median Follow up of 22 months, mean ± SD overall survival (OS) was 65.391 ± 4.705. Kaplan–Meier analysis showed that patients positive for mTOR and CXCR4 expression had shorter DFS (p = .01 & .02) and OS (p = .02 & .04). Multivariate analysis showed that CXCR4 and mTOR positivity is an independent prognostic factor for significantly poorer DFS (p = .03, and .02 respectively) but not for OS (p = .09 and .08 respectively) in the DLBCL pateints.Conclusion: Our results indicate that the expression of CXCR4 and mTOR may be poor prognostic biomarkers in DLBCL.

scholarly journals De Novo CD5+ Primary Gastrointestinal Diffuse Large B-Cell Lymphoma: Challenges With Treatment and Clinical Course

2019 ◽  
Vol 7 ◽  
pp. 232470961989354
Author(s):  
Preethi Ramachandran ◽  
Sonu Sahni ◽  
Jen C. Wang
Keyword(s):  
Gastrointestinal Tract ◽  
B Cell ◽  
De Novo ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Gastrointestinal Lymphomas ◽  
Large B Cell

The gastrointestinal tract is a common extranodal site for lymphomas. However, primary gastrointestinal lymphomas are rare. Diffuse large B-cell lymphomas (DLBCL) are the most commonly encountered type in the gastrointestinal tract. Most of the DLBCL are CD5 negative. CD5+ DLBCL is very rare and a poor prognostic subtype of lymphoma. We report a rare case of primary small bowel CD5+ DLBCL that evolved from being a localized low International Prognostic Index–scored disease into an advanced and aggressive disease primarily dictated by the presence of CD5 antigen positivity.

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